cancer related thesis

DigitalCommons@UNMC

Home > Eppley Institute > Theses & Dissertations

Theses & Dissertations: Cancer Research

Theses/dissertations from 2024 2024.

Therapeutic Effects of BET Protein Inhibition in B-cell Malignancies and Beyond , Audrey L. Smith

Identification of Mitotic Phosphatases and Cyclin K as Novel Molecular Targets in Pancreatic Cancer , Yi Xiao

Theses/Dissertations from 2023 2023

Development of Combination Therapy Strategies to Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors , Nicholas Mullen

Overcoming Resistance Mechanisms to CDK4/6 Inhibitor Treatment Using CDK6-Selective PROTAC , Sarah Truong

Theses/Dissertations from 2022 2022

Omics Analysis in Cancer and Development , Emalie J. Clement

Investigating the Role of Splenic Macrophages in Pancreatic Cancer , Daisy V. Gonzalez

Polymeric Chloroquine in Metastatic Pancreatic Cancer Therapy , Rubayat Islam Khan

Evaluating Targets and Therapeutics for the Treatment of Pancreatic Cancer , Shelby M. Knoche

Characterization of 1,1-Diarylethylene FOXM1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells , Cassie Liu

Novel Mechanisms of Protein Kinase C α Regulation and Function , Xinyue Li

SOX2 Dosage Governs Tumor Cell Identity and Proliferation , Ethan P. Metz

Post-Transcriptional Control of the Epithelial-to-Mesenchymal Transition (EMT) in Ras-Driven Colorectal Cancers , Chaitra Rao

Use of Machine Learning Algorithms and Highly Multiplexed Immunohistochemistry to Perform In-Depth Characterization of Primary Pancreatic Tumors and Metastatic Sites , Krysten Vance

Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient , Megan E. Wackel

Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling , Pauline Xu

Phos-Tag-Based Screens Identify Novel Therapeutic Targets in Ovarian Cancer and Pancreatic Cancer , Renya Zeng

Theses/Dissertations from 2021 2021

Functional Characterization of Cancer-Associated DNA Polymerase ε Variants , Stephanie R. Barbari

Pancreatic Cancer: Novel Therapy, Research Tools, and Educational Outreach , Ayrianne J. Crawford

Apixaban to Prevent Thrombosis in Adult Patients Treated With Asparaginase , Krishna Gundabolu

Molecular Investigation into the Biologic and Prognostic Elements of Peripheral T-cell Lymphoma with Regulators of Tumor Microenvironment Signaling Explored in Model Systems , Tyler Herek

Utilizing Proteolysis-Targeting Chimeras to Target the Transcriptional Cyclin-Dependent Kinases 9 and 12 , Hannah King

Insights into Cutaneous Squamous Cell Carcinoma Pathogenesis and Metastasis Using a Bedside-to-Bench Approach , Marissa Lobl

Development of a MUC16-Targeted Near-Infrared Antibody Probe for Fluorescence-Guided Surgery of Pancreatic Cancer , Madeline T. Olson

FGFR4 glycosylation and processing in cholangiocarcinoma promote cancer signaling , Andrew J. Phillips

Theses/Dissertations from 2020 2020

Cooperativity of CCNE1 and FOXM1 in High-Grade Serous Ovarian Cancer , Lucy Elge

Characterizing the critical role of metabolic and redox homeostasis in colorectal cancer , Danielle Frodyma

Genomic and Transcriptomic Alterations in Metabolic Regulators and Implications for Anti-tumoral Immune Response , Ryan J. King

Dimers of Isatin Derived Spirocyclic NF-κB Inhibitor Exhibit Potent Anticancer Activity by Inducing UPR Mediated Apoptosis , Smit Kour

From Development to Therapy: A Panoramic Approach to Further Our Understanding of Cancer , Brittany Poelaert

The Cellular Origin and Molecular Drivers of Claudin-Low Mammary Cancer , Patrick D. Raedler

Mitochondrial Metabolism as a Therapeutic Target for Pancreatic Cancer , Simon Shin

Development of Fluorescent Hyaluronic Acid Nanoparticles for Intraoperative Tumor Detection , Nicholas E. Wojtynek

Theses/Dissertations from 2019 2019

The role of E3 ubiquitin ligase FBXO9 in normal and malignant hematopoiesis , R. Willow Hynes-Smith

BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response , Kimiko L. Krieger

Targeted Inhibition of Histone Deacetyltransferases for Pancreatic Cancer Therapy , Richard Laschanzky

Human Leukocyte Antigen (HLA) Class I Molecule Components and Amyloid Precursor-Like Protein 2 (APLP2): Roles in Pancreatic Cancer Cell Migration , Bailee Sliker

Theses/Dissertations from 2018 2018

FOXM1 Expression and Contribution to Genomic Instability and Chemoresistance in High-Grade Serous Ovarian Cancer , Carter J. Barger

Overcoming TCF4-Driven BCR Signaling in Diffuse Large B-Cell Lymphoma , Keenan Hartert

Functional Role of Protein Kinase C Alpha in Endometrial Carcinogenesis , Alice Hsu

Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer , Beth Neilsen

Elucidating the Roles of Lunatic Fringe in Pancreatic Ductal Adenocarcinoma , Prathamesh Patil

Theses/Dissertations from 2017 2017

Metabolic Reprogramming of Pancreatic Ductal Adenocarcinoma Cells in Response to Chronic Low pH Stress , Jaime Abrego

Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer , Katie L. Bailey

The Role of EHD2 in Triple-Negative Breast Cancer Tumorigenesis and Progression , Timothy A. Bielecki

Perturbing anti-apoptotic proteins to develop novel cancer therapies , Jacob Contreras

Role of Ezrin in Colorectal Cancer Cell Survival Regulation , Premila Leiphrakpam

Evaluation of Aminopyrazole Analogs as Cyclin-Dependent Kinase Inhibitors for Colorectal Cancer Therapy , Caroline Robb

Identifying the Role of Janus Kinase 1 in Mammary Gland Development and Breast Cancer , Barbara Swenson

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice , Garland Michael Upchurch

Theses/Dissertations from 2016 2016

EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor , Luke R. Cypher

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma , Darci M. Fink

Role of CBL-family Ubiquitin Ligases as Critical Negative Regulators of T Cell Activation and Functions , Benjamin Goetz

Exploration into the Functional Impact of MUC1 on the Formation and Regulation of Transcriptional Complexes Containing AP-1 and p53 , Ryan L. Hanson

DNA Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent of Error-Prone Synthesis, and the Role of dNTP Pools , Olga V. Kochenova

Defining the Role of Phosphorylation and Dephosphorylation in the Regulation of Gap Junction Proteins , Hanjun Li

Molecular Mechanisms Regulating MYC and PGC1β Expression in Colon Cancer , Jamie L. McCall

Pancreatic Cancer Invasion of the Lymphatic Vasculature and Contributions of the Tumor Microenvironment: Roles for E-selectin and CXCR4 , Maria M. Steele

Altered Levels of SOX2, and Its Associated Protein Musashi2, Disrupt Critical Cell Functions in Cancer and Embryonic Stem Cells , Erin L. Wuebben

Theses/Dissertations from 2015 2015

Characterization and target identification of non-toxic IKKβ inhibitors for anticancer therapy , Elizabeth Blowers

Effectors of Ras and KSR1 dependent colon tumorigenesis , Binita Das

Characterization of cancer-associated DNA polymerase delta variants , Tony M. Mertz

A Role for EHD Family Endocytic Regulators in Endothelial Biology , Alexandra E. J. Moffitt

Biochemical pathways regulating mammary epithelial cell homeostasis and differentiation , Chandrani Mukhopadhyay

EPACs: epigenetic regulators that affect cell survival in cancer. , Catherine Murari

Role of the C-terminus of the Catalytic Subunit of Translesion Synthesis Polymerase ζ (Zeta) in UV-induced Mutagensis , Hollie M. Siebler

LGR5 Activates TGFbeta Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

LGR5 Activates TGFβ Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

Theses/Dissertations from 2014 2014

Genetic dissection of the role of CBL-family ubiquitin ligases and their associated adapters in epidermal growth factor receptor endocytosis , Gulzar Ahmad

Strategies for the identification of chemical probes to study signaling pathways , Jamie Leigh Arnst

Defining the mechanism of signaling through the C-terminus of MUC1 , Roger B. Brown

Targeting telomerase in human pancreatic cancer cells , Katrina Burchett

The identification of KSR1-like molecules in ras-addicted colorectal cancer cells , Drew Gehring

Mechanisms of regulation of AID APOBEC deaminases activity and protection of the genome from promiscuous deamination , Artem Georgievich Lada

Characterization of the DNA-biding properties of human telomeric proteins , Amanda Lakamp-Hawley

Studies on MUC1, p120-catenin, Kaiso: coordinate role of mucins, cell adhesion molecules and cell cycle players in pancreatic cancer , Xiang Liu

Epac interaction with the TGFbeta PKA pathway to regulate cell survival in colon cancer , Meghan Lynn Mendick

Theses/Dissertations from 2013 2013

Deconvolution of the phosphorylation patterns of replication protein A by the DNA damage response to breaks , Kerry D. Brader

Modeling malignant breast cancer occurrence and survival in black and white women , Michael Gleason

The role of dna methyltransferases in myc-induced lymphomagenesis , Ryan A. Hlady

Design and development of inhibitors of CBL (TKB)-protein interactions , Eric A. Kumar

Pancreatic cancer-associated miRNAs : expression, regulation and function , Ashley M. Mohr

Mechanistic studies of mitochondrial outer membrane permeabilization (MOMP) , Xiaming Pang

Novel roles for JAK2/STAT5 signaling in mammary gland development, cancer, and immune dysregulation , Jeffrey Wayne Schmidt

Optimization of therapeutics against lethal pancreatic cancer , Joshua J. Souchek

Theses/Dissertations from 2012 2012

Immune-based novel diagnostic mechanisms for pancreatic cancer , Michael J. Baine

Sox2 associated proteins are essential for cell fate , Jesse Lee Cox

KSR2 regulates cellular proliferation, transformation, and metabolism , Mario R. Fernandez

Discovery of a novel signaling cross-talk between TPX2 and the aurora kinases during mitosis , Jyoti Iyer

Regulation of metabolism by KSR proteins , Paula Jean Klutho

The role of ERK 1/2 signaling in the dna damage-induced G2 , Ryan Kolb

Regulation of the Bcl-2 family network during apoptosis induced by different stimuli , Hernando Lopez

Studies on the role of cullin3 in mitosis , Saili Moghe

Characteristics of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer and Ewing's sarcoma , Haley Louise Capek Peters

Structural and biophysical analysis of a human inosine triphosphate pyrophosphatase polymorphism , Peter David Simone

Functions and regulation of Ron receptor tyrosine kinase in human pancreatic cancer and its therapeutic applications , Yi Zou

Theses/Dissertations from 2011 2011

Coordinate detection of new targets and small molecules for cancer therapy , Kurt Fisher

The role of c-Myc in pancreatic cancer initiation and progression , Wan-Chi Lin

The role of inosine triphosphate pyrophosphatase (ITPA) in maintanence [sic] of genomic stability in human cells , Miriam-Rose Menezes

Molecular insights into major histocompatibility complex class I folding and assembly , Laura Christina Simone

The role of bcl-2 in colon cancer metastatic progression , Wang Wang

• Eppley Institute Website
• McGoogan Library

Advanced Search

• Notify me via email or RSS
• Collections
• Disciplines

Author Corner

Home | About | FAQ | My Account | Accessibility Statement

Privacy Copyright

• Help & Terms of Use
• Elizabeth Blackwell Institute for Health Research
• Phone 00 44 117 455 6360
• Email [email protected]
• Website http://www.bristol.ac.uk/cancer

United Kingdom

Student theses

• 1 - 50 out of 131 results
• Title (descending)

Search results

A biologically-inspired artificial lateral line: observations of collective behaviour in fish lead to the development of a novel design of simple and low-cost artificial lateral line sensor.

Supervisor: Hauert, S. (Supervisor), Ioannou, C. (Supervisor) & Genner, M. J. (Supervisor)

Student thesis : Doctoral Thesis › Doctor of Philosophy (PhD)

A characterisation of mononuclear phagocyte dynamics in the healthy and regenerating zebrafish heart

Supervisor: Richardson, B. (Supervisor) & Martin, P. B. (Supervisor)

A Computational Framework for the Optimisation of Antivenom Pharmacokinetics and Pharmacodynamics

Supervisor: Hauert, S. (Supervisor), Blee, J. A. (Supervisor) & Collinson, I. R. (Supervisor)

An Epigenome-Wide Association Study of Eczema

Supervisor: Paternoster, L. (Supervisor), Elliott, H. (Supervisor) & Relton, C. (Supervisor)

Student thesis : Master's Thesis › Master of Science by Research (MScR)

An Investigation into the Link Between Sleep and Alzheimer’s Disease Using a Multi-Method Approach

Supervisor: Coulthard, E. J. (Supervisor) & Ben-Shlomo, Y. (Supervisor)

Applications of HS-AFM Imaging to Marine Microbial Life and its Environment

Supervisor: Day, J. C. C. (Supervisor), Picco, L. M. (Supervisor), Payton, O. D. (Supervisor) & Allen, M. (Supervisor)

Applying ‘omics to understand and predict juvenile idiopathic arthritis

Supervisor: Relton, C. (Supervisor), Ramanan, A. (Supervisor), Sharp, G. (Supervisor) & Zhou, Y. (External person) (Supervisor)

Appraising the causal relationship between DNA methylation and type 2 diabetes

Supervisor: Elliott, H. (Supervisor), Relton, C. (Supervisor) & Sharp, G. (Supervisor)

A qualitative exploration of recruiters' and patients' perspectives and experiences of the recruitment encounter in randomised controlled trials

Supervisor: Young, B. (Supervisor), Rooshenas, L. (Supervisor), Elliott, D. (Supervisor), Jepson, M. (Supervisor) & Donovan , J. L. (Supervisor)

Arole for IGFBP-2 in DNA repair in breast cancer cells

Supervisor: Perks, C. (Supervisor), Holly, J. (Supervisor) & Biernacka, K. M. (Supervisor)

Assessing the feasibility of dietary restriction, including short-term fasting, at the time of chemotherapy

Supervisor: Atkinson, C. (Supervisor), Herbert, G. (Supervisor), Ness, A. (Supervisor) & Perks, C. (Supervisor)

A study of hyperspectral reflectance and fluorescence imaging as alternative Methods for assessing coral health

Supervisor: Day, J. (Supervisor) & Scott, T. (Supervisor)

Biological and lifestyle predictors of survival in head and neck cancer.

Supervisor: Dos Santos Ferreira, D. (Supervisor), Ingle, S. (Supervisor), Ness, A. (Supervisor), Martin, R. (Supervisor) & May, M. T. (Supervisor)

Biosynthetic Studies on Kalimantacin Antibiotics

Supervisor: Willis, C. L. (Supervisor) & Crump, M. P. (Supervisor)

Capturing complexity, comorbidity and frailty in people with parkinsonism and understanding their impact

Supervisor: Ben-Shlomo, Y. (Supervisor) & Henderson, E. (Supervisor)

Causal implications of common infections and platelet function on cardiovascular disease

Supervisor: Paternoster, L. (Supervisor), Richmond, R. (Supervisor), Davey Smith, G. (Supervisor) & Poole, A. (Supervisor)

Causal pathways from cognitive ability to Alzheimer's disease

Supervisor: Davies, N. M. (Supervisor), Anderson, E. L. (Supervisor), Howe, L. D. (Supervisor) & Ben-Shlomo, Y. (Supervisor)

Characterisation of Ataxia Telangiectasia Mutated in RPE-1 cells and its role in cellular sensitivity to hypo-osmotic stress

Supervisor: Mellor, H. H. (Supervisor) & Wood, W. J. (Supervisor)

Characterisation of the cellular compartments containing inhibitory receptors in CD8 + T cells

Supervisor: Wuelfing, C. (Supervisor) & Morgan, D. (Supervisor)

Characterisation of the HELLS and Irc5 subfamily of chromatin remodellers

Supervisor: Dillingham, M. (Supervisor) & Chambers, A. (Supervisor)

Characterising Red Cell-Derived Vesicles in Sickle Cell Disease and Investigating Potential to Induce Tolerance to Human Red Cell Antigens

Supervisor: Blair, A. (Supervisor) & Anstee, D. J. (Supervisor)

Complex trait architecture through the lens of epigenome-wide association studies

Supervisor: Gaunt, T. (Supervisor), Hemani, G. (Supervisor) & Timpson, N. J. (Supervisor)

Decentralised Algorithms for Area Coverage

Supervisor: Ganesh, A. (Supervisor) & Hauert, S. (Supervisor)

Dental care pathways and parent-reported dental outcomes for 5-year-old children born with a cleft in the UK

Supervisor: Fowler, P. V. (Supervisor), Leary, S. D. (Supervisor), Wren, Y. E. (Supervisor) & Williams, J. (Supervisor)

Student thesis : Doctoral Thesis › Doctor of Dental Surgery (DDS)

Diabetes mellitus causes adiposopathy in bone marrow: investigation of the underpinning cellular and molecular mechanisms

Supervisor: Madeddu, P. (Supervisor) & Mellor, H. H. (Supervisor)

Does the association between later eating rhythm and childhood adiposity differ between the UK and China?

Supervisor: Leary, S. D. (Supervisor) & Northstone, K. (Supervisor)

Does the IGF axis influence EMT to play a role in bladder cancer progression?

Supervisor: Perks, C. (Supervisor) & Holly, J. M. P. (Supervisor)

Elucidating mechanisms of tumour resistance to checkpoint blockade

Supervisor: Wooldridge, L. (Supervisor), Morgan, D. (Supervisor) & Wuelfing, C. (Supervisor)

Enhanced numerical techniques for time domain electromagnetic analysis

Evaluation of a primary care epilepsy specialist nurse service.

Supervisor: Bachmann, M. (Supervisor)

Evaluation of Cardiopulmonary Exercise Testing (CPET) as a Prognostic Tool in Idiopathic Pulmonary Fibrosis (IPF)

Supervisor: Maskell, N. (Supervisor) & Millar, A. (Supervisor)

Evolving Morphological Adaption Methods in Compliant Robots

Supervisor: Hauser, H. (Supervisor) & Hauert, S. (Supervisor)

Examining the Role of Placental-derived MicroRNA Secretions in Response to Gestational Hypoxia on Foetal Neurodevelopment

Supervisor: Case, C. P. (Supervisor), Perks, C. M. (Supervisor), Uney, J. B. (Supervisor) & Fulga, T. A. (External person) (Supervisor)

Expertise during surgical innovation: advancing understanding about non-technical skills and related optimisation factors

Supervisor: Mills, N. (Supervisor), Blencowe, N. (Supervisor) & Blazeby, J. (Supervisor)

Exploring the effect of adiposity on platelet function and related pathways: implications for cardiovascular disease

Supervisor: Timpson, N. (Supervisor) & Hers, I. (Supervisor)

Exploring the in vitro behaviour of endothelial cells in different cell culture models

Supervisor: Mellor, H. (Supervisor) & Gaston, K. (Supervisor)

Exploring the microclot-driven pre-metastatic niche: live imaging studies in zebrafish larvae

Supervisor: Martin, P. B. (Supervisor) & Nobes, C. D. (Supervisor)

Exploring the role of BCL-3 in colorectal cancer cell therapeutic resistance

Supervisor: Martin, P. (Supervisor), Cullen, P. (Supervisor) & Williams, A. (Supervisor)

Extra-pulmonary effects of lung function and lung disease

Supervisor: Davey Smith, G. (Supervisor), Dodd, J. (Supervisor) & Granell, R. (Supervisor)

Fatty acid construction within the biosynthesis of the polyketide antibiotic mupirocin

Supervisor: Crump, M. P. (Supervisor), Willis, C. (External person) (Supervisor) & Race, P. R. (Supervisor)

Feeding and Autoimmunity in Children with Down’s Syndrome Evaluation Study (FADES)

Supervisor: Hamilton-Shield, J. P. (Supervisor), Gillespie, K. M. (Supervisor) & Leary, S. D. (Supervisor)

From peptide oligomers to single-chain proteins

Supervisor: Woolfson, D. (Supervisor) & Crump, M. (Supervisor)

Genetic and Environmental Contributions to Trajectories of Depressive Symptoms

Supervisor: Manley, D. (Supervisor), Timpson, N. J. (Supervisor) & Leckie, G. (Supervisor)

Genetic and epidemiologic approaches to elucidate the role of abnormal hip shape in the development of hip osteoarthritis

Supervisor: Davey Smith, G. (Supervisor) & Tobias, J. (Supervisor)

Genetic and epigenetic data as a tool to augment understanding of oropharyngeal cancer

Supervisor: Relton, C. L. (Supervisor), Thomas, S. J. (Supervisor), Richmond, R. C. (Supervisor) & Elliott, H. R. (Supervisor)

Geographical gene-environment interaction and correlation for mental health in the UK and Sweden

Supervisor: Davis, O. S. (Supervisor) & Davey Smith, G. (Supervisor)

Glial autophagy capability and the control of neuroinflammatory signaling in Parkinson’s disease.

Supervisor: Lane, J. D. (Supervisor) & Carroll, B. M. (Supervisor)

'Hi-Fi Nanoscience' : Exploring the nanoscale with optical pickup units

Supervisor: Payton, O. D. (Supervisor) & Day, J. C. C. (Supervisor)

High-throughput proteomic analysis of the dengue virus secretome and the identification of plasma biomarkers of disease severity

Supervisor: Morgan, D. (Supervisor) & Davidson, A. (Supervisor)

Identification of Protein Disulphide-Isomerase A3 Dependent Proteins from the Secretome of MDA-MB-231 Breast Cancer Cells

Supervisor: Adams, J. (Supervisor)

UKnowledge > College of Medicine > Toxicology and Cancer Biology > Theses & Dissertations

Theses and Dissertations--Toxicology and Cancer Biology

Theses/dissertations from 2024 2024.

Elucidation of Mismatch Repair Regulation by ABL1: Advantages/Disadvantages of Tyrosine Kinase Inhibitor Treatment , Hannah Daniels

ACQUIRED TREATMENT RESISTANCE IN PROSTATE CANCER VIA THE PRODUCTION OF RADIATION DERIVED EXTRACELLULAR VESICLES CONTAINING MITOCHONDRIAL PROTEINS , Caitlin Miller

Theses/Dissertations from 2023 2023

ELUCIDATING THE FUNCTIONAL IMPORTANCE OF PEROXIREDOXIN IV IN PROSTATE CANCER AND ITS SECRETION MECHANISM , Na Ding

Targeting EZH2 to Improve Outcomes of Lung Squamous Cell Carcinoma , Tanner DuCote

UNDERSTANDING AND TARGETING THE TPH1-SEROTONIN-HTR3A AXIS IN SMALL CELL LUNG CANCER , Yanning Hao

CONSERVED NOVEL INTERACTIONS BETWEEN POST-REPLICATIVE REPAIR AND MISMATCH REPAIR PROTEINS HAVE DIFFERENTIAL EFFECTS ON DNA REPAIR PATHWAYS , Anna K. Miller

UNDERSTANDING THE ROLE OF PEROXIREDOXIN IV IN COLORECTAL CANCER DEVELOPMENT , Pratik Thapa

BEYOND MITOSIS, PLK1-MEDIATED PHOSPHORYLATION RE-WIRES CANCER METABOLISM AND PROMOTES CANCER PROGRESSION , Qiongsi Zhang

Theses/Dissertations from 2022 2022

ELUCIDATING THE ROLE OF POLYCOMB REPRESSIVE COMPLEX 2 IN LUNG STEM CELL FATE AND LUNG DISEASE , Aria Byrd

SEX DIMORPHISM IN HEMATOPOIESIS AND BONE MARROW NICHE , xiaojing cui

EXTRACELLULAR VESICLES AND CANCER THERAPY: AN INSIGHT INTO THE ROLE OF OXIDATIVE STRESS , Jenni Ho

OVERCOMING RESISTANCE TO SG-ARIS IN CASTRATION-RESISTANT PROSTATE CANCER , Chaohao Li

Theses/Dissertations from 2021 2021

THE TUMOR SUPPRESSOR PAR-4 REGULATES HYPERTROPHIC OBESITY , Nathalia Araujo

Epigenetic States Regulate Tumor Aggressiveness and Response to Targeted Therapies in Lung Adenocarcinoma , Fan Chen

DELINEATING THE ROLE OF FATTY ACID METABOLISM TO IMPROVE THERAPEUTIC STRATEGIES FOR COLORECTAL CANCER , James Drury

DEVELOPMENT OF TOOLS FOR ATOM-LEVEL INTERPRETATION OF STABLE ISOTOPE-RESOLVED METABOLOMICS DATASETS , Huan Jin

MECHANISMS OF CADMIUM-INDUCED AND EPIDERMAL GROWTH FACTOR RECEPTOR MUTATION-DRIVEN LUNG TUMORIGENESIS , Hsuan-Pei Lin

SCIENCE-BASED REGULATION OF PHARMACOLOGICAL SUBSTANCES IN COMPETITION HORSES , Jacob Machin

A NOVEL ROLE FOR NEUROTENSIN IN REGULATION OF STEM CELL FUNCTION IN THE SMALL INTESTINE , Stephanie Rock

Theses/Dissertations from 2020 2020

NOVEL POST-TRANSLATIONAL MODIFICATION AND FUNCTION OF FUS: THE RELEVANCE TO AMYOTROPHIC LATERAL SCLEROSIS , Alexandra Arenas

Prostate Cancer Resistance to Cabazitaxel Chemotherapy , Diane Begemann

Examining the Role of Metabolic Pathways as Therapeutic Modalities for Triple Negative Breast Cancer , Jeremy Andrew Johnson

THE ROLE OF NEURAL PRECURSOR CELL EXPRESSED DEVELOPMENTALLY DOWN-REGULATED PROTEIN 9 IN ENHANCED AGGRESSIVENESS OF HEXAVALENT CHROMIUM TRANSFORMED BRONCHIAL EPITHELIAL CELLS , Peter Van Wie

Theses/Dissertations from 2019 2019

A COMPROMISED LIVER ALTERS PCB TOXICITY AND NUTRIENT METABOLISM , Jazmyne D. L. Barney

Advanced Search

• Notify me via email or RSS

Browse by Author

• Collections
• Disciplines

Author Corner

• Submit Research

New Title Here

Below. --> connect.

• Law Library
• Special Collections
• Copyright Resource Center
• Graduate School
• Scholars@UK

• We’d like your feedback

Home | About | FAQ | My Account | Accessibility Statement

Privacy Copyright

University of Kentucky ®

An Equal Opportunity University Accreditation Directory Email Privacy Policy Accessibility Disclosures

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Review Article
• Published: 22 April 2024

Cancer cell metabolism and antitumour immunity

• Mara De Martino   ORCID: orcid.org/0000-0002-3049-6495 1 ,
• Jeffrey C. Rathmell 2 ,
• Lorenzo Galluzzi 1 , 3 , 4 &
• Claire Vanpouille-Box   ORCID: orcid.org/0000-0001-7213-0670 1 , 3  

Nature Reviews Immunology ( 2024 ) Cite this article

38 Altmetric

Metrics details

• Cancer microenvironment
• Tumour immunology

Accumulating evidence suggests that metabolic rewiring in malignant cells supports tumour progression not only by providing cancer cells with increased proliferative potential and an improved ability to adapt to adverse microenvironmental conditions but also by favouring the evasion of natural and therapy-driven antitumour immune responses. Here, we review cancer cell-intrinsic and cancer cell-extrinsic mechanisms through which alterations of metabolism in malignant cells interfere with innate and adaptive immune functions in support of accelerated disease progression. Further, we discuss the potential of targeting such alterations to enhance anticancer immunity for therapeutic purposes.

This is a preview of subscription content, access via your institution

Access options

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

24,99 € / 30 days

cancel any time

Subscribe to this journal

Receive 12 print issues and online access

195,33 € per year

only 16,28 € per issue

Buy this article

• Purchase on Springer Link
• Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Metabolism of immune cells in cancer

The immunometabolic ecosystem in cancer

Metabolic barriers to cancer immunotherapy

Hanahan, D. Hallmarks of cancer: new dimensions. Cancer Discov. 12 , 31–46 (2022).

Article   CAS   PubMed   Google Scholar  

Izzo, L. T., Affronti, H. C. & Wellen, K. E. The bidirectional relationship between cancer epigenetics and metabolism. Annu. Rev. Cancer Biol. 5 , 235–257 (2021).

Article   PubMed   Google Scholar  

Pirozzi, C. J. & Yan, H. The implications of IDH mutations for cancer development and therapy. Nat. Rev. Clin. Oncol. 18 , 645–661 (2021).

Kerk, S. A., Papagiannakopoulos, T., Shah, Y. M. & Lyssiotis, C. A. Metabolic networks in mutant KRAS-driven tumours: tissue specificities and the microenvironment. Nat. Rev. Cancer 21 , 510–525 (2021).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Kruiswijk, F., Labuschagne, C. F. & Vousden, K. H. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat. Rev. Mol. Cell Biol. 16 , 393–405 (2015).

Vitale, I., Shema, E., Loi, S. & Galluzzi, L. Intratumoral heterogeneity in cancer progression and response to immunotherapy. Nat. Med. 27 , 212–224 (2021).

Singleton, D. C., Macann, A. & Wilson, W. R. Therapeutic targeting of the hypoxic tumour microenvironment. Nat. Rev. Clin. Oncol. 18 , 751–772 (2021).

Petroni, G., Buqué, A., Coussens, L. M. & Galluzzi, L. Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment. Nat. Rev. Drug. Discov. 21 , 440–462 (2022).

Stine, Z. E., Schug, Z. T., Salvino, J. M. & Dang, C. V. Targeting cancer metabolism in the era of precision oncology. Nat. Rev. Drug. Discov. 21 , 141–162 (2022).

Warburg, O., Posener, K. & Negelein, E. Über den stoffwechsel der carcinomzelle [German]. Naturwissenschaften 12 , 1131–1137 (1924).

Article   CAS   Google Scholar  

Debnath, J., Gammoh, N. & Ryan, K. M. Autophagy and autophagy-related pathways in cancer. Nat. Rev. Mol. Cell Biol. 24 , 560–575 (2023).

Kim, J. & DeBerardinis, R. J. Mechanisms and implications of metabolic heterogeneity in cancer. Cell Metab. 30 , 434–446 (2019).

Kroemer, G., Chan, T. A., Eggermont, A. M. M. & Galluzzi, L. Immunosurveillance in clinical cancer management. CA Cancer J. Clin. 74 , 187–202 (2024).

Klapp, V. et al. The DNA damage response and inflammation in cancer. Cancer Discov. 13 , 1521–1545 (2023).

Kroemer, G., Galassi, C., Zitvogel, L. & Galluzzi, L. Immunogenic cell stress and death. Nat. Immunol. 23 , 487–500 (2022).

Voss, K. et al. A guide to interrogating immunometabolism. Nat. Rev. Immunol. 21 , 637–652 (2021).

Bantug, G. R. & Hess, C. The immunometabolic ecosystem in cancer. Nat. Immunol. 24 , 2008–2020 (2023).

Leone, R. D. & Powell, J. D. Metabolism of immune cells in cancer. Nat. Rev. Cancer 20 , 516–531 (2020).

Lunt, S. Y. & Vander Heiden, M. G. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 27 , 441–464 (2011).

Chang, C. H. et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 162 , 1229–1241 (2015).

Reinfeld, B. I. et al. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature 593 , 282–288 (2021). This article elegantly shows that intratumoural myeloid cells have increased glucose uptake compared with malignant cells.

Cascone, T. et al. Increased tumor glycolysis characterizes immune resistance to adoptive T cell therapy. Cell Metab. 27 , 977–987.e4 (2018).

Guo, D. et al. Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IκBα. Cell Metab. 34 , 1312–1324.e6 (2022).

Li, W. et al. Aerobic glycolysis controls myeloid-derived suppressor cells and tumor immunity via a specific CEBPB isoform in triple-negative breast cancer. Cell Metab. 28 , 87–103.e6 (2018).

Wu, L. et al. Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNF-α. Cell Metab. 35 , 1580–1596.e9 (2023).

Galluzzi, L., Kepp, O., Vander Heiden, M. G. & Kroemer, G. Metabolic targets for cancer therapy. Nat. Rev. Drug. Discov. 12 , 829–846 (2013).

Claps, G. et al. The multiple roles of LDH in cancer. Nat. Rev. Clin. Oncol. 19 , 749–762 (2022).

Elia, I. et al. Tumor cells dictate anti-tumor immune responses by altering pyruvate utilization and succinate signaling in CD8 + T cells. Cell Metab. 34 , 1137–1150.e6 (2022).

Quinn, W. J. et al. Lactate limits T cell proliferation via the NAD(H) redox state. Cell Rep. 33 , 108500 (2020).

Ma, J. et al. Lithium carbonate revitalizes tumor-reactive CD8 + T cells by shunting lactic acid into mitochondria. Nat. Immunol. 25 , 552–561 (2024).

Brand, A. et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. 24 , 657–671 (2016).

Oshima, N. et al. Dynamic imaging of LDH inhibition in tumors reveals rapid in vivo metabolic rewiring and vulnerability to combination therapy. Cell Rep. 30 , 1798–1810.e4 (2020).

Rundqvist, H. et al. Cytotoxic T-cells mediate exercise-induced reductions in tumor growth. eLife 9 , e59996 (2020).

Feng, Q. et al. Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity. Nat. Commun. 13 , 4981 (2022). This report shows that lactate may mediate immunostimulatory effects by promoting CD8 + T cell stemness.

Angelin, A. et al. Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments. Cell Metab. 25 , 1282–1293.e7 (2017).

Kumagai, S. et al. Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer Cell 40 , 201–218.e9 (2022).

Watson, M. J. et al. Metabolic support of tumour-infiltrating regulatory T cells by lactic acid. Nature 591 , 645–651 (2021).

Gu, J. et al. Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells. Cell Rep. 39 , 110986 (2022).

Xiong, J. et al. Lactylation-driven METTL3-mediated RNA m 6 A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol. Cell 82 , 1660–1677.e10 (2022).

Zappasodi, R. et al. CTLA-4 blockade drives loss of T reg stability in glycolysis-low tumours. Nature 591 , 652–658 (2021). This work is the first demonstration that CTLA4 blockers are particularly effective at destabilizing T reg cells in tumours with limited glycolytic activity.

Chen, P. et al. Gpr132 sensing of lactate mediates tumor–macrophage interplay to promote breast cancer metastasis. Proc. Natl Acad. Sci. USA 114 , 580–585 (2017).

Qian, Y. et al. MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma. Cancer Cell 41 , 1363–1380.e7 (2023).

Pittet, M. J., Michielin, O. & Migliorini, D. Clinical relevance of tumour-associated macrophages. Nat. Rev. Clin. Oncol. 19 , 402–421 (2022).

Pietrocola, F., Galluzzi, L., Bravo-San Pedro, J. M., Madeo, F. & Kroemer, G. Acetyl coenzyme A: a central metabolite and second messenger. Cell Metab. 21 , 805–821 (2015).

Sullivan, L. B., Gui, D. Y. & Vander Heiden, M. G. Altered metabolite levels in cancer: implications for tumour biology and cancer therapy. Nat. Rev. Cancer 16 , 680–693 (2016).

Cheng, J. et al. Cancer-cell-derived fumarate suppresses the anti-tumor capacity of CD8 + T cells in the tumor microenvironment. Cell Metab. 35 , 961–978.e10 (2023).

Zecchini, V. et al. Fumarate induces vesicular release of mtDNA to drive innate immunity. Nature 615 , 499–506 (2023). This article elegantly shows that the accumulation of fumarate as elicited by mutation of fumarate hydratase causes mitochondrial disruption coupled with cGAS activation.

Li, J. et al. Non-cell-autonomous cancer progression from chromosomal instability. Nature 620 , 1080–1088 (2023).

Vanpouille-Box, C., Demaria, S., Formenti, S. C. & Galluzzi, L. Cytosolic DNA sensing in organismal tumor control. Cancer Cell 34 , 361–378 (2018).

Mangalhara, K. C. et al. Manipulating mitochondrial electron flow enhances tumor immunogenicity. Science 381 , 1316–1323 (2023).

Gomez, V. et al. Breast cancer-associated macrophages promote tumorigenesis by suppressing succinate dehydrogenase in tumor cells. Sci. Signal 13 , eaax4585 (2020).

Notarangelo, G. et al. Oncometabolite d -2HG alters T cell metabolism to impair CD8 + T cell function. Science 377 , 1519–1529 (2022).

Bunse, L. et al. Suppression of antitumor T cell immunity by the oncometabolite ( R )-2-hydroxyglutarate. Nat. Med. 24 , 1192–1203 (2018). Together with Notarangelo et al. (2022), this work provides mechanistic insights into the ability of the oncometabolite D -2HG to mediate robust immunosuppressive effects.

Minogue, E. et al. Glutarate regulates T cell metabolism and anti-tumour immunity. Nat. Metab. 5 , 1747–1764 (2023).

Miller, K. D. et al. Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer. Nat. Cancer 4 , 1491–1507 (2023).

Bachem, A. et al. Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8 + T cells. Immunity 51 , 285–297.e5 (2019).

Ryan, D. G. et al. Coupling Krebs cycle metabolites to signalling in immunity and cancer. Nat. Metab. 1 , 16–33 (2019).

Zhao, H. et al. Myeloid-derived itaconate suppresses cytotoxic CD8 + T cells and promotes tumour growth. Nat. Metab. 4 , 1660–1673 (2022).

Olagnier, D. et al. Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming. Nat. Commun. 9 , 3506 (2018).

Article   PubMed   PubMed Central   Google Scholar  

Hoy, A. J., Nagarajan, S. R. & Butler, L. M. Tumour fatty acid metabolism in the context of therapy resistance and obesity. Nat. Rev. Cancer 21 , 753–766 (2021).

Duman, C. et al. Acyl-CoA-binding protein drives glioblastoma tumorigenesis by sustaining fatty acid oxidation. Cell Metab. 30 , 274–289.e5 (2019).

Jiang, N. et al. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion. Nat. Commun. 13 , 1511 (2022).

Mariño, G. et al. Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol. Cell 53 , 710–725 (2014).

Liu, Z. et al. CPT1A-mediated fatty acid oxidation confers cancer cell resistance to immune-mediated cytolytic killing. Proc. Natl Acad. Sci. USA 120 , e2302878120 (2023).

Harel, M. et al. Proteomics of melanoma response to immunotherapy reveals mitochondrial dependence. Cell 179 , 236–250.e18 (2019).

Luo, J., Yang, H. & Song, B. L. Mechanisms and regulation of cholesterol homeostasis. Nat. Rev. Mol. Cell Biol. 21 , 225–245 (2020).

Anderson, H. A., Hiltbold, E. M. & Roche, P. A. Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat. Immunol. 1 , 156–162 (2000).

Bi, K. et al. Antigen-induced translocation of PKC-θ to membrane rafts is required for T cell activation. Nat. Immunol. 2 , 556–563 (2001).

Wang, G. et al. Arf1-mediated lipid metabolism sustains cancer cells and its ablation induces anti-tumor immune responses in mice. Nat. Commun. 11 , 220 (2020).

Röhrig, F. & Schulze, A. The multifaceted roles of fatty acid synthesis in cancer. Nat. Rev. Cancer 16 , 732–749 (2016).

Xu, S. et al. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8 + T cells in tumors. Immunity 54 , 1561–1577.e7 (2021).

Ma, X. et al. CD36-mediated ferroptosis dampens intratumoral CD8 + T cell effector function and impairs their antitumor ability. Cell Metab. 33 , 1001–1012.e5 (2021). Together with Xu et al. (2021), this work implicates the uptake of oxidized lipids by CD8 + T cells via the scavenger receptor CD36 in the establishment of intratumoural immunosuppression.

Jiang, L., Fang, X., Wang, H., Li, D. & Wang, X. Ovarian cancer-intrinsic fatty acid synthase prevents anti-tumor immunity by disrupting tumor-infiltrating dendritic cells. Front. Immunol. 9 , 2927 (2018).

Wang, H. et al. CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors. Nat. Immunol. 21 , 298–308 (2020).

Ao, Y. Q. et al. Tumor-infiltrating CD36 + CD8 + T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer. BMC Cancer 23 , 367 (2023).

Accioly, M. T. et al. Lipid bodies are reservoirs of cyclooxygenase-2 and sites of prostaglandin-E 2 synthesis in colon cancer cells. Cancer Res. 68 , 1732–1740 (2008).

Huang, Q. et al. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat. Med. 17 , 860–866 (2011).

Zelenay, S. et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell 162 , 1257–1270 (2015).

Bayerl, F. et al. Tumor-derived prostaglandin E 2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses. Immunity 56 , 1341–1358.e11 (2023).

Bottcher, J. P. et al. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell 172 , 1022–1037.e14 (2018).

Wei, J. et al. The COX-2–PGE 2 pathway promotes tumor evasion in colorectal adenomas. Cancer Prev. Res. 15 , 285–296 (2022).

Goto, S. et al. Upregulation of PD-L1 expression by prostaglandin E 2 and the enhancement of IFN-γ by anti-PD-L1 antibody combined with a COX-2 inhibitor in Mycoplasma bovis infection. Front. Vet. Sci. 7 , 12 (2020).

Sajiki, Y. et al. Prostaglandin E 2 -induced immune exhaustion and enhancement of antiviral effects by anti-PD-L1 antibody combined with COX-2 inhibitor in bovine leukemia virus infection. J. Immunol. 203 , 1313–1324 (2019).

Sarkar, O. S. et al. Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy. Sci. Adv. 9 , eadg3736 (2023).

Zhang, B. et al. MFSD2A potentiates gastric cancer response to anti-PD-1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response. Cancer Commun. 43 , 1097–1116 (2023).

Article   Google Scholar  

Mullen, N. J. & Singh, P. K. Nucleotide metabolism: a pan-cancer metabolic dependency. Nat. Rev. Cancer 23 , 275–294 (2023).

Lee, J. S. et al. Urea cycle dysregulation generates clinically relevant genomic and biochemical signatures. Cell 174 , 1559–1570.e22 (2018).

Elliott, M. R. et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461 , 282–286 (2009).

Chekeni, F. B. et al. Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature 467 , 863–867 (2010). Together with Elliott et al. (2009), this report is the first to document the ability of extracellular nucleotides including ATP to function as chemoattractants for myeloid cells.

Ma, Y. et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 38 , 729–741 (2013).

Ghiringhelli, F. et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nat. Med. 15 , 1170–1178 (2009).

Thompson, E. A. & Powell, J. D. Inhibition of the adenosine pathway to potentiate cancer immunotherapy: potential for combinatorial approaches. Annu. Rev. Med. 72 , 331–348 (2021).

Kepp, O. et al. ATP and cancer immunosurveillance. EMBO J. 40 , e108130 (2021).

Cluntun, A. A., Lukey, M. J., Cerione, R. A. & Locasale, J. W. Glutamine metabolism in cancer: understanding the heterogeneity. Trends Cancer 3 , 169–180 (2017).

Edwards, D. N. et al. Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer. J. Clin. Invest. 131 , e140100 (2021).

Leone, R. D. et al. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science 366 , 1013–1021 (2019). This article elegantly shows that pharmacological inhibition of glutaminase in the TME can robustly impair cancer cell metabolism while sparing CD8 + T cells.

Oh, M. H. et al. Targeting glutamine metabolism enhances tumor-specific immunity by modulating suppressive myeloid cells. J. Clin. Invest. 130 , 3865–3884 (2020).

Guo, C. et al. SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity. Nature 620 , 200–208 (2023).

Wang, Z. et al. Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion. Nat. Commun. 13 , 6308 (2022).

Sanderson, S. M., Gao, X., Dai, Z. & Locasale, J. W. Methionine metabolism in health and cancer: a nexus of diet and precision medicine. Nat. Rev. Cancer 19 , 625–637 (2019).

Hung, M. H. et al. Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma. Nat. Commun. 12 , 1455 (2021).

Fang, L. et al. Methionine restriction promotes cGAS activation and chromatin untethering through demethylation to enhance antitumor immunity. Cancer Cell 41 , 1118–1133.e12 (2023).

Bian, Y. et al. Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. Nature 585 , 277–282 (2020).

Huang, Y. et al. A bimetallic nanoplatform for STING activation and CRISPR/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses. Nat. Commun. 14 , 4647 (2023).

Xue, Y. et al. Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade. Nat. Commun. 14 , 4758 (2023).

Xue, C. et al. Tryptophan metabolism in health and disease. Cell Metab. 35 , 1304–1326 (2023).

Fallarino, F. et al. T cell apoptosis by tryptophan catabolism. Cell Death Differ. 9 , 1069–1077 (2002).

Chen, W., Liang, X., Peterson, A. J., Munn, D. H. & Blazar, B. R. The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J. Immunol. 181 , 5396–5404 (2008).

Sonner, J. K. et al. The stress kinase GCN2 does not mediate suppression of antitumor T cell responses by tryptophan catabolism in experimental melanomas. Oncoimmunology 5 , e1240858 (2016).

Munn, D. H. et al. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med. 189 , 1363–1372 (1999).

Kesarwani, P. et al. Quinolinate promotes macrophage-induced immune tolerance in glioblastoma through the NMDAR/PPARγ signaling axis. Nat. Commun. 14 , 1459 (2023).

Yuan, H. et al. Lysine catabolism reprograms tumour immunity through histone crotonylation. Nature 617 , 818–826 (2023).

Lemberg, K. M., Gori, S. S., Tsukamoto, T., Rais, R. & Slusher, B. S. Clinical development of metabolic inhibitors for oncology. J. Clin. Invest. 132 , e148550 (2022).

Galluzzi, L., Humeau, J., Buque, A., Zitvogel, L. & Kroemer, G. Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat. Rev. Clin. Oncol. 17 , 725–741 (2020).

Petroni, G., Buque, A., Zitvogel, L., Kroemer, G. & Galluzzi, L. Immunomodulation by targeted anticancer agents. Cancer Cell 39 , 310–345 (2021).

Galluzzi, L., Aryankalayil, M. J., Coleman, C. N. & Formenti, S. C. Emerging evidence for adapting radiotherapy to immunotherapy. Nat. Rev. Clin. Oncol. 20 , 543–557 (2023).

Zheng, J. B. et al. Glucose metabolism inhibitor PFK-015 combined with immune checkpoint inhibitor is an effective treatment regimen in cancer. Oncoimmunology 11 , 2079182 (2022).

Redman, R. A., Pohlmann, P. R., Kurman, M. R., Tapolsky, G. & Chesney, J. A. A phase I, dose-escalation, multi-center study of PFK-158 in patients with advanced solid malignancies explores a first-in-man inhbibitor of glycolysis. J. Clin. Oncol. 33 , TPS2606 (2015).

Halford, S. et al. A phase I dose-escalation study of AZD3965, an oral monocarboxylate transporter 1 inhibitor, in patients with advanced cancer. Clin. Cancer Res. 29 , 1429–1439 (2023).

Babl, N. et al. MCT4 blockade increases the efficacy of immune checkpoint blockade. J. Immunother. Cancer 11 , e007349 (2023).

Lopez, E. et al. Inhibition of lactate transport by MCT-1 blockade improves chimeric antigen receptor T-cell therapy against B-cell malignancies. J. Immunother. Cancer 11 , e006287 (2023).

Rodriguez-Ruiz, M. E., Vitale, I., Harrington, K. J., Melero, I. & Galluzzi, L. Immunological impact of cell death signaling driven by radiation on the tumor microenvironment. Nat. Immunol. 21 , 120–134 (2020).

Cytlak, U. M. et al. Immunomodulation by radiotherapy in tumour control and normal tissue toxicity. Nat. Rev. Immunol. 22 , 124–138 (2022).

Wicker, C. A. et al. Glutaminase inhibition with telaglenastat (CB-839) improves treatment response in combination with ionizing radiation in head and neck squamous cell carcinoma models. Cancer Lett. 502 , 180–188 (2021).

Boysen, G. et al. Glutaminase inhibitor CB-839 increases radiation sensitivity of lung tumor cells and human lung tumor xenografts in mice. Int. J. Radiat. Biol. 95 , 436–442 (2019).

Varghese, S. et al. The glutaminase inhibitor CB-839 (Telaglenastat) enhances the antimelanoma activity of T-cell-mediated immunotherapies. Mol. Cancer Ther. 20 , 500–511 (2021).

Lee, C. H. et al. Telaglenastat plus everolimus in advanced renal cell carcinoma: a randomized, double-blinded, placebo-controlled, phase II ENTRATA trial. Clin. Cancer Res. 28 , 3248–3255 (2022).

Meric-Bernstam, F. et al. Telaglenastat plus cabozantinib or everolimus for advanced or metastatic renal cell carcinoma: an open-label phase I trial. Clin. Cancer Res. 28 , 1540–1548 (2022).

Tannir, N. M. et al. Efficacy and safety of telaglenastat plus cabozantinib vs placebo plus cabozantinib in patients with advanced renal cell carcinoma: the CANTATA randomized clinical trial. JAMA Oncol. 8 , 1411–1418 (2022).

Byun, J. K. et al. Inhibition of glutamine utilization synergizes with immune checkpoint inhibitor to promote antitumor immunity. Mol. Cell 80 , 592–606.e8 (2020).

Vitale, I. et al. Apoptotic cell death in disease-current understanding of the NCCD 2023. Cell Death Differ. 30 , 1097–1154 (2023).

Platten, M., Nollen, E. A. A., Rohrig, U. F., Fallarino, F. & Opitz, C. A. Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat. Rev. Drug. Discov. 18 , 379–401 (2019).

Kraehenbuehl, L., Weng, C. H., Eghbali, S., Wolchok, J. D. & Merghoub, T. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. Nat. Rev. Clin. Oncol. 19 , 37–50 (2022).

Jochems, C. et al. The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells. Oncotarget 7 , 37762–37772 (2016).

Mitchell, T. C. et al. Epacadostat plus pembrolizumab in patients with advanced solid tumors: phase I results from a multicenter, open-label phase I/II trial (ECHO-202/KEYNOTE-037). J. Clin. Oncol. 36 , 3223–3230 (2018).

Long, G. V. et al. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 20 , 1083–1097 (2019).

Clement, C. C. et al. 3-Hydroxy- l -kynurenamine is an immunomodulatory biogenic amine. Nat. Commun. 12 , 4447 (2021).

[No authors listed]. Companies scaling back IDO1 inhibitor trials. Cancer Discov. 8 , Of5 (2018).

Shi, D. et al. USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer. Nat. Commun. 13 , 5644 (2022).

Michaud, M. et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 334 , 1573–1577 (2011). This study reports the first demonstration that pre-mortem autophagic responses are essential for the release of ATP by dying cancer cells.

Ohta, A. et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc. Natl Acad. Sci. USA 103 , 13132–13137 (2006).

Young, A. et al. Co-inhibition of CD73 and A2AR adenosine signaling improves anti-tumor immune responses. Cancer Cell 30 , 391–403 (2016).

Tang, T. et al. Transcriptional control of pancreatic cancer immunosuppression by metabolic enzyme CD73 in a tumor-autonomous and -autocrine manner. Nat. Commun. 14 , 3364 (2023).

Wennerberg, E. et al. CD73 blockade promotes dendritic cell infiltration of irradiated tumors and tumor rejection. Cancer Immunol. Res. 8 , 465–478 (2020).

Beavis, P. A. et al. Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy. J. Clin. Invest. 127 , 929–941 (2017).

Beavis, P. A. et al. Adenosine receptor 2A blockade increases the efficacy of anti-PD-1 through enhanced antitumor T-cell responses. Cancer Immunol. Res. 3 , 506–517 (2015).

Mittal, D. et al. Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor. Cancer Res. 74 , 3652–3658 (2014).

Chiappori, A. A. et al. Phase I study of taminadenant (PBF509/NIR178), an adenosine 2A receptor antagonist, with or without spartalizumab (PDR001), in patients with advanced non-small cell lung cancer. Clin. Cancer Res. 28 , 2313–2320 (2022).

Lim, E. A. et al. Phase Ia/b, open-label, multicenter study of AZD4635 (an adenosine A2A receptor antagonist) as monotherapy or combined with durvalumab, in patients with solid tumors. Clin. Cancer Res. 28 , 4871–4884 (2022).

Cascone, T. et al. Neoadjuvant durvalumab alone or combined with novel immuno-oncology agents in resectable lung cancer: the phase II NeoCOAST platform trial. Cancer Discov. 13 , 2394–2411 (2023).

Herbst, R. S. et al. COAST: an open-label, phase II, multidrug platform study of durvalumab alone or in combination with oleclumab or monalizumab in patients with unresectable, stage III non-small-cell lung cancer. J. Clin. Oncol. 40 , 3383–3393 (2022).

Falchook, G. et al. First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors. EClinicalMedicine 34 , 100797 (2021).

Kelly, W. et al. Phase II investigation of TVB-2640 (denifanstat) with bevacizumab in patients with first relapse high-grade astrocytoma. Clin. Cancer Res. 29 , 2419–2425 (2023).

Tang, R. et al. Targeting neoadjuvant chemotherapy-induced metabolic reprogramming in pancreatic cancer promotes anti-tumor immunity and chemo-response. Cell Rep. Med. 4 , 101234 (2023).

Francica, B. J. et al. Dual blockade of EP2 and EP4 signaling is required for optimal immune activation and antitumor activity against prostaglandin-expressing tumors. Cancer Res. Commun. 3 , 1486–1500 (2023).

Wang, Y. et al. Combination of EP 4 antagonist MF-766 and anti-PD-1 promotes anti-tumor efficacy by modulating both lymphocytes and myeloid cells. Oncoimmunology 10 , 1896643 (2021).

Chen, J. S. et al. CC-01 (chidamide plus celecoxib) modifies the tumor immune microenvironment and reduces tumor progression combined with immune checkpoint inhibitor. Sci. Rep. 12 , 1100 (2022).

Chan, J. P. et al. The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain. PLoS Biol. 16 , e2006443 (2018).

Boergesen, M. et al. Genome-wide profiling of liver X receptor, retinoid X receptor, and peroxisome proliferator-activated receptor α in mouse liver reveals extensive sharing of binding sites. Mol. Cell Biol. 32 , 852–867 (2012).

Hou, Y. et al. SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing. Immunity 56 , 2492–2507.e10 (2023).

Dai, J. et al. Acetylation blocks cGAS activity and inhibits self-DNA-induced autoimmunity. Cell 176 , 1447–1460.e14 (2019). This report documents the ability of aspirin to block cGAS signalling by non-enzymatic acetylation.

Arber, N. et al. Celecoxib for the prevention of colorectal adenomatous polyps. N. Engl. J. Med. 355 , 885–895 (2006).

Mitchell, M. J. et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug. Discov. 20 , 101–124 (2021).

De Martino, M. et al. Radiation therapy promotes unsaturated fatty acids to maintain survival of glioblastoma. Cancer Lett. 570 , 216329 (2023).

Dagogo-Jack, I. & Shaw, A. T. Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 15 , 81–94 (2018).

Gengenbacher, N., Singhal, M. & Augustin, H. G. Preclinical mouse solid tumour models: status quo, challenges and perspectives. Nat. Rev. Cancer 17 , 751–765 (2017).

Chuprin, J. et al. Humanized mouse models for immuno-oncology research. Nat. Rev. Clin. Oncol. 20 , 192–206 (2023).

Park, J., Morley, T. S., Kim, M., Clegg, D. J. & Scherer, P. E. Obesity and cancer — mechanisms underlying tumour progression and recurrence. Nat. Rev. Endocrinol. 10 , 455–465 (2014).

Sepich-Poore, G. D. et al. The microbiome and human cancer. Science 371 , eabc4552 (2021).

Yang, L. et al. Targeting stromal glutamine synthetase in tumors disrupts tumor microenvironment-regulated cancer cell growth. Cell Metab. 24 , 685–700 (2016).

Mishra, R. et al. Stromal epigenetic alterations drive metabolic and neuroendocrine prostate cancer reprogramming. J. Clin. Invest. 128 , 4472–4484 (2018).

Sousa, C. M. et al. Erratum: pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature 540 , 150 (2016).

Olivares, O. et al. Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat. Commun. 8 , 16031 (2017).

Schwörer, S. et al. Proline biosynthesis is a vent for TGFβ-induced mitochondrial redox stress. EMBO J. 39 , e103334 (2020).

Nieman, K. M. et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med. 17 , 1498–1503 (2011).

Lee, P., Chandel, N. S. & Simon, M. C. Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat. Rev. Mol. Cell Biol. 21 , 268–283 (2020).

Terme, M. et al. VEGFA–VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res. 73 , 539–549 (2013).

Allard, B., Allard, D., Buisseret, L. & Stagg, J. The adenosine pathway in immuno-oncology. Nat. Rev. Clin. Oncol. 17 , 611–629 (2020).

Vignali, P. D. A. et al. Hypoxia drives CD39-dependent suppressor function in exhausted T cells to limit antitumor immunity. Nat. Immunol. 24 , 267–279 (2023).

Sattiraju, A. et al. Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression. Immunity 56 , 1825–1843.e6 (2023).

Park, J. H. et al. Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors. Nat. Immunol. 22 , 336–346 (2021).

Klionsky, D. J. et al. Autophagy in major human diseases. EMBO J. 40 , e108863 (2021).

Clarke, A. J. & Simon, A. K. Autophagy in the renewal, differentiation and homeostasis of immune cells. Nat. Rev. Immunol. 19 , 170–183 (2019).

Yamazaki, T. et al. Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy. Nat. Immunol. 21 , 1160–1171 (2020).

Poillet-Perez, L. et al. Autophagy promotes growth of tumors with high mutational burden by inhibiting a T-cell immune response. Nat. Cancer 1 , 923–934 (2020).

Yamamoto, K. et al. Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature 581 , 100–105 (2020). Together with Yamazaki et al. (2020) and Poillet-Perez et al. (2020), this work documents various mechanisms by which autophagic responses in malignant cells mediate robust immunosuppressive effects.

Baginska, J. et al. Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia. Proc. Natl Acad. Sci. USA 110 , 17450–17455 (2013).

Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R. & Kroemer, G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat. Rev. Drug. Discov. 16 , 487–511 (2017).

Levy, J. M. M., Towers, C. G. & Thorburn, A. Targeting autophagy in cancer. Nat. Rev. Cancer 17 , 528–542 (2017).

Download references

Acknowledgements

M.D.M. is supported by the Future Leaders 2023 Postdoctoral Fellowship from the Brain Tumour Charity (#BTC224874-01). J.C.R. receives support related to this work from an R01 grant from the National Institutes of Health National Cancer Institute (NIH/NCI) (#CA217987). Among other funds, L.G. is/has been supported by an R01 grant from the NIH/NCI (#CA271915) and two Breakthrough Level 2 grants from the US Department of Defense (DoD) Breast Cancer Research Program (BCRP) (#BC180476P1, #BC210945). Among other funds, C.V.-B. is supported by an R01 grant from the NHI National Institute of Neurological Disorders and Stroke (NIH/NINDS) (#NS131945-01) and an R21 grant from the NIH/NCI (#CA280787-01).

Author information

Authors and affiliations.

Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA

Mara De Martino, Lorenzo Galluzzi & Claire Vanpouille-Box

Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA

Jeffrey C. Rathmell

Sandra and Edward Meyer Cancer Center, New York, NY, USA

Lorenzo Galluzzi & Claire Vanpouille-Box

Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA

Lorenzo Galluzzi

You can also search for this author in PubMed   Google Scholar

Contributions

C.V.-B. and L.G. conceived the article. M.D.M., C.V.-B. and L.G. wrote the first version of the manuscript with constructive input from J.C.R. M.D.M. prepared display items under supervision from C.V.-B. and L.G. All authors approved the submitted version of the article.

Corresponding authors

Correspondence to Lorenzo Galluzzi or Claire Vanpouille-Box .

Ethics declarations

Competing interests.

J.C.R. is a founder and scientific advisory board member of Sitryx Therapeutics. L.G. is/has been holding research contracts with Lytix Biopharma, Promontory and Onxeo; has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, Onxeo, The Longevity Labs, Inzen, Imvax, Sotio, Promontory, Noxopharm, EduCom and the Luke Heller TECPR2 Foundation; and holds Promontory stock options. The other authors declare no competing interests.

Peer review

Peer review information.

Nature Reviews Immunology thanks C. Dang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information.

A set of metabolic pathways that build large molecules from smaller units in support of cell growth and proliferation.

A lysosome-dependent catabolic pathway that ensures the degradation of supernumerary, dysfunctional or potentially cytotoxic cytoplasmic material.

(CAFs). A heterogeneous population of fibroblasts that define the tumour stroma and communicate with both malignant and immune components of the tumour microenvironment.

A set of metabolic pathways that break down large molecules into smaller units for recycling or for the production of ATP.

The post-translational modification of lysine residues by crotonyl-CoA.

A metabolic cascade converting acetyl-CoA into long-chain lipids for cellular anabolism.

(ICIs). Monoclonal antibodies targeting co-inhibitory T cell receptors in support of restored anticancer immunosurveillance.

The post-translational modification of lysine residues by lactate.

(MDSCs). Poorly differentiated myeloid cells with prominent immunosuppressive and tumour-promoting properties.

(OXPHOS). A mitochondrial pathway, fed by NADH and succinate provided by the tricarboxylic acid cycle (TCA cycle), that generates ATP from a series of oxidation reactions that culminate with the generation of H 2 O.

A metabolic shunt that diverts glycolytic intermediates towards the synthesis of nucleotides, some amino acids and antioxidants.

A state of T cell dysfunction that arises during many chronic infections and cancer.

(TCA cycle). A mitochondrial circuit that ensures adequate levels of key metabolites involved in several catabolic and anabolic reactions, including acetyl-CoA, pyruvate, oxaloacetate, succinate and α-ketoglutarate.

(TAMs). A heterogeneous and plastic population of intratumoural macrophages with a spectrum of activity ranging from prominently antitumour (so-called M1-like TAMs) to prominently pro-tumour (so-called M2-like TAMs). Caution should be made when extrapolating these in vitro-defined M1 and M2 phenotypes to in vivo settings.

A metabolic pathway to convert excess ammonia into urea for excretion.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Cite this article.

De Martino, M., Rathmell, J.C., Galluzzi, L. et al. Cancer cell metabolism and antitumour immunity. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-01026-4

Download citation

Accepted : 18 March 2024

Published : 22 April 2024

DOI : https://doi.org/10.1038/s41577-024-01026-4

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

• Open access
• Published: 26 November 2018

The 150 most important questions in cancer research and clinical oncology series: questions 94–101

Edited by Cancer Communications

Cancer Communications

Cancer Communications volume  38 , Article number:  69 ( 2018 ) Cite this article

23k Accesses

8 Citations

1 Altmetric

Metrics details

Since the beginning of 2017, Cancer Communications (former title: Chinese Journal of Cancer ) has published a series of important questions regarding cancer research and clinical oncology, to provide an enhanced stimulus for cancer research, and to accelerate collaborations between institutions and investigators. In this edition, the following 8 valuable questions are presented. Question 94. The origin of tumors: time for a new paradigm? Question 95. How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma? Question 96. Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor? Question 97. What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction? Question 98. Is high local concentration of metformin essential for its anti-cancer activity? Question 99. How can we monitor the emergence of cancer cells anywhere in the body through plasma testing? Question 100. Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells? Question 101. Is cell migration a selectable trait in the natural evolution of carcinoma?

Until now, the battle against cancer is still ongoing, but there are also ongoing discoveries being made. Milestones in cancer research and treatments are being achieved every year; at a quicker pace, as compared to decades ago. Likewise, some cancers that were considered incurable are now partly curable, lives that could not be saved are now being saved, and for those with yet little options, they are now having best-supporting care. With an objective to promote worldwide cancer research and even accelerate inter-countries collaborations, since the beginning of 2017, Cancer Communications (former title: Chinese Journal of Cancer ) has launched a program of publishing 150 most important questions in cancer research and clinical oncology [ 1 ]. We are providing a platform for researchers to freely voice-out their novel ideas, and propositions to enhance the communications on how and where our focus should be placed [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. In this edition, 8 valuable and inspiring questions, Question 94–101, from highly distinguished professionals from different parts of the world are presented. If you have any novel proposition(s) and Question(s), please feel free to contact Ms. Ji Ruan via email: [email protected].

Question 94: The origin of tumors: time for a new paradigm?

Background and implications.

“There is no worse blind man than the one who doesn’t want to see. There is no worse deaf man than the one who doesn’t want to hear. And there is no worse madman than the one who doesn’t want to understand.” —Ancient Proverb

In the past half-century, cancer biologists have focused on a dogma in which cancer was viewed as a proliferative disease due to mechanisms that activate genes (oncogenes) to promote cell proliferation or inactivate genes (tumor suppressor genes) to suppress tumor growth. In retrospect, these concepts were established based on functional selections, by using tissue culture (largely mouse NIH 3T3 cells) for the selection of transformed foci at the time when we knew virtually nothing about the human genome [ 14 ]. However, it is very difficult to use these genes individually or in combinations to transform primary human cells. Further, the simplified view of uncontrolled proliferation cannot explain the tumor as being a malignant organ or a teratoma, as observed by pathologists over centuries. Recently, the cancer genomic atlas project has revealed a wide variety of genetic alterations ranging from no mutation to multiple chromosomal deletions or fragmentations, which make the identification of cancer driver mutations very challenging in a background of such a massive genomic rearrangement. Paradoxically, this increase the evidences demonstrating that the oncogenic mutations are commonly found in many normal tissues, further challenging the dogma that genetic alteration is the primary driver of this disease.

Logically, the birth of a tumor should undergo an embryonic-like development at the beginning, similar to that of a human. However, the nature of such somatic-derived early embryo has been elusive. Recently, we provided evidence to show that polyploid giant cancer cells (PGCCs), which have been previously considered non-dividing, are actually capable of self-renewal, generating viable daughter cells via amitotic budding, splitting and burst, and capable of acquisition of embryonic-like stemness [ 15 , 16 , 17 ]. The mode of PGCC division is remarkably similar to that of blastomere, a first step in human embryogenesis following fertilization. The blastomere nucleus continuously divides 4–5 times without cytoplasmic division to generate 16–32 cells and then to form compaction/morulae before developing into a blastocyst [ 18 ]. Based on these data and similarity to the earliest stage of human embryogenesis, I propose a new theory that tumor initiation can be achieved via a dualistic origin, similar to the first step of human embryogenesis via the formation of blastomere-like cells, i.e. the activation of blastomere or blastomere-like cells which leads to the dedifferentiation of germ cells or somatic cells, respectively, which is then followed by the differentiation to generate their respective stem cells, and the differentiation arrest at a specific developmental hierarchy leading to tumor initiation [ 19 ]. The somatic-derived blastomere-like cancer stem cell follows its own mode of cell growth and division and is named as the giant cell cycle. This cycle includes four distinct but overlapping phases: the initiation, self-renewal, termination, and stability phases. The giant cell cycle can be tracked in vitro and in vivo due to their salient giant cell morphology (Fig.  1 ).

One mononucleated polyploid giant cancer cell (PGCC) in the background of regular size diploid cancer cells. The PGCC can be seen to be at least 100 times larger than that of regular cancer cells

This new theory challenges the traditional paradigm that cancer is a proliferative disease, and proposes that the initiation of cancer requires blastomere-like division that is similar to that of humans before achieving stable proliferation at specific developmental hierarchy in at least half of all human cancers. This question calls for all investigators in the cancer research community to investigate the role of PGCCs in the initiation, progression, resistance, and metastasis of cancer and to look for novel agents to block the different stages of the giant cell cycle.

The histopathology (phenotype) of cancers has been there all the time. It is just the theory of cancer origin proposed by scientists that changes from time to time. After all, trillions of dollars have been invested in fighting this disease by basing on its genetic origin in the past half-century, yet, little insight has been gained [ 14 ]. Here are two quotes from Einstein: “Insanity: doing the same thing over and over again expecting different results”, and “We cannot solve our problems with the same thinking we used when created them”.

In short, it is time to change our mindset and to start pursuing PGCCs, which we can observe under the microscope. But with very little understanding about these cells, it is time for a shift in paradigm.

Jinsong Liu.

Affiliation

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4095, USA.

Email address

[email protected]

Question 95: How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the world with a dismal 5-year overall survival rate of less than 5%; which has not been significantly improved since the past decades. Although surgical resection is the only option for curative treatment of PDAC, only 15%–20% of patients with PDAC have the chance to undergo curative resection, leaving the rest with only palliative options in hope for increasing their quality of life; since they were already at unresectable and non-curative stages at their first diagnosis.

The lack of specific symptoms in the early-stage of PDAC is responsible for rendering an early diagnosis difficult. Therefore, more sensitive and specific screening methodologies for its early detection is urgently needed to improve its diagnosis, starting early treatments, and ameliorating prognoses. The diagnosis so far relies on imaging modalities such as abdominal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP), and positron emission tomography (PET). One may propose to screen for pancreatic cancer in high-risk populations, which is highly recommended, however screening intervention for all the people is not a wise choice; when considering the relatively low prevalence of PDAC, and the difficulty for diagnosing it in its early stage [ 20 ].

Therefore, alternative diagnostic tools for early detection of PDAC are highly expected. Among the biomarkers currently used in clinical practice, carbohydrate antigen 19–9 (CA19–9) is among the most useful one for supporting the diagnosis of PDAC, but it is neither sufficiently sensitive nor specific for its early detection. Yachida et al. reported in 2010 that the initiating mutation in the pancreas occurs approximately two decades before the PDAC to start growing in distant organs [ 21 ], which indicates a broad time of the window of opportunity for the early detection of PDAC. With the advancement in next-generation sequencing technology, the number of reported studies regarding novel potential molecular biomarkers in bodily fluids including the blood, feces, urine, saliva, and pancreatic juice for early detection of PDAC has been increasing. Such biomarkers may be susceptible to detect mutations at the genetic or epigenetic level, identifying important non-coding RNA (especially microRNA and long non-coding RNA), providing insights regarding the metabolic profiles, estimating the tumor level in liquid biopsies (circulating free DNA, circulating tumor cells and exosomes), and so on.

Another approach to identifying biomarkers for the early detection of pancreatic cancer is using animal models. In spontaneous animal models of pancreatic cancer, such as Kras-mutated mouse models, it is expected that by high throughput analyses of the genetic/epigenetic/proteomic alterations, some novel biomarkers might be able to be identified. For instance, Sharma et al. reported in 2017 that the detection of phosphatidylserine-positive exosomes enabled the diagnosis of early-stage malignancies in LSL-Kras G12D , Cdkn2a lox/lox : p48 Cre and LSL-Kras G12d/+ , LSL-Trp R172H/+ , and P48 Cre mice [ 22 ].

These analyses in clinical samples or animal models hold the clues for the early detection of PDAC, however, further studies are required to validate their diagnostic performance. What’s most important, will be the lining-up of these identified prospective biomarkers, to validate their sensitivities and specificities. This will determine their potential for widespread clinical applicability, and hopefully, accelerate the early diagnosis of PDAC.

Mikiya Takao 1,2 , Hirotaka Matsuo 2 , Junji Yamamoto 1 , and Nariyoshi Shinomiya 2 .

1 Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan; 2 Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

E-mail address

[email protected]; [email protected]; [email protected]; [email protected]

Question 96: Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers, and nearly half of the patients had metastatic PDAC when they are initially diagnosed. When they are accompanied by metastatic tumors, unlike most solid cancer, PDAC cannot be cured with primary surgical resection alone [ 23 , 24 ]. Also, since PDAC has poor responses to conventional therapies, improvements in adjunctive treatment approach including chemo- and immuno-therapy are earnestly required. From this standpoint, recent results regarding the differences in the molecular evolution of pancreatic cancer subtypes provide a new insight into its therapeutic development [ 25 ], which may lead to the improvement of the prognosis of not only metastatic PDAC but also of locally advanced or recurrent PDAC.

In fact, new chemotherapeutic regimens such as the combination of gemcitabine with nab-paclitaxel and FOLFIRINOX have been reported to show improved prognosis despite a lack of examples of past successes in the treatment of patients with metastatic PDAC who had undergone R0 resection [ 26 ]. While many mutations including KRAS , CDKN2A , TP53, and SMAD4 are associated with pancreatic carcinogenesis, no effective molecular targeted drug has been introduced in the clinical setting so far. A recent report of a phase I/II study on refametinib, a MEK inhibitor, indicated that KRAS mutation status might affect the overall response rate, disease control rate, progression-free survival, and overall survival of PDAC in combination with gemcitabine [ 27 ].

While immunotherapy is expected to bring a great improvement in cancer treatment, until now, immune checkpoint inhibitors have achieved limited clinical benefit for patients with PDAC. This might be because PDAC creates a uniquely immunosuppressive tumor microenvironment, where tumor-associated immunosuppressive cells and accompanying desmoplastic stroma prevent the tumor cells from T cell infiltration. Recently reported studies have indicated that immunotherapy might be effective when combined with focal adhesion kinase (FAK) inhibitor [ 28 ] or IL-6 inhibitor [ 29 ], but more studies are required to validate their use in clinical practice.

As such, we believe that if the dynamic monitoring of drug sensitivity/resistance in the individual patients is coupled with precision treatment based on individualized genetics/epigenetics/proteomics alterations in the patients’ tumor, this could improve the treatment outcomes of PDAC.

Mikiya Takao 1,2 , Hirotaka Matsuo 2 , Junji Yamamoto 1 , and Nariyoshi Shinomiya 2.

Question 97: What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?

Recently, cancer immunotherapy has shown great clinical benefit in multiple types of cancers [ 30 , 31 , 32 ]. It has provided new approaches for cancer treatment. However, it has been observed that only a fraction of patients respond to immunotherapy.

Much effort has been made to identify markers for immunotherapeutic response. Tumor mutation burden (TMB), mismatch repair (MMR) deficiency, PD-L1 expression, and tumor infiltration lymphocyte (TIL) have been found to be associated with an increased response rate in checkpoint blockade therapies. Unfortunately, a precise prediction is still challenging in this field. Moreover, when to stop the treatment of immunotherapy is an urgent question that remains to be elucidated.

In other words, there is no available approach to determine if a patient has generated a good immune response against the cancer after immunotherapy treatments. All of these indicate the complexity and challenges that reside for implementing novel man-induced cancer-effective immune response therapeutics. A variety of immune cells play collaborative roles at different stages to recognize antigens and eventually to generate an effective anti-cancer immune response. Given the high complexity of the immune system, a rational evaluation approach is needed to cover the whole process. Moreover, we need to perfect vaccine immunization and/or in vitro activation of T cells to augment the function of the immune system; particularly the formation of immune memory.

Edison Liu 1 , Penghui Zhou 2 , Jiang Li 2 .

1 The Jackson Laboratory, Bar Harbor, ME 04609, USA; 2 Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.

[email protected]; [email protected]; [email protected]

Question 98: Is high local concentration of metformin essential for its anti-cancer activity?

Metformin was approved as a first line of anti-diabetic drug since decades. Interestingly, the fact that clinical epidemiological studies have shown that metformin can reduce the risk of a variety of cancers stimulates considerable recognition to explore its anticancer activity.

Although the in vitro and in vivo experimental results have demonstrated that metformin can have some potential anti-tumor effects, more than 100 clinical trials did not achieve such desirable results [ 33 ]. We and others believe that the main problem resides in the prescribing doses used. For cancer treatment, a much higher dose may be needed for observing any anti-tumor activities, as compared to the doses prescribed for diabetics [ 34 , 35 , 36 ].

Further, if the traditional local/oral administration approach is favored, the prescribed metformin may not be at the required dose-concentration once it reaches the blood to have the effective anti-cancer activities. We, therefore, propose that intravesical instillation of metformin into the bladder lumen could be a promising way to treat for bladder cancer, at least. We have already obtained encouraging results both in vitro and in vivo experiments, including in an orthotopical bladder cancer model [ 36 , 37 ]. Now, we are waiting to observe its prospective clinical outcome.

Mei Peng 1 , Xiaoping Yang 2 .

1 Department of Pharmacy, Xiangya Hospital, Central South University. Changsha, Hunan 410083, P. R. China; 2 Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, P. R. China.

[email protected]; [email protected]

Question 99: How can we monitor the emergence of cancer cells anywhere in the body through plasma testing?

The early detection of cancer is still a relentless worldwide challenge. The sensitivity and specificity of traditional blood tumor markers and imaging technologies are still to be greatly improved. Hence, novel approaches for the early detection of cancer are urgently needed.

The emergence of liquid biopsy technologies opens a new driveway for solving such issues. According to the definition of the National Cancer Institute of the United States, a liquid biopsy is a test done on a sample of blood to look for tumorigenic cancer cells or pieces of tumor cells’ DNA that are circulating in the blood [ 38 ]. This definition implies two main types of the current liquid biopsy: one that detects circulating tumor cells and the other that detects non-cellular material in the blood, including tumor DNA, RNA, and exosomes.

Circulating tumor cells (CTCs) are referred to as tumor cells that have been shed from the primary tumor location and have found their way to the peripheral blood. CTCs were first described in 1869 by an Australian pathologist, Thomas Ashworth, in a patient with metastatic cancer [ 39 ]. The importance of CTCs in modern cancer research began in the mid-1990s with the demonstration that CTCs exist early in the course of the disease.

It is estimated that there are about 1–10 CTCs per mL in whole blood of patients with metastatic cancer, even fewer in patients with early-stage cancer [ 40 ]. For comparison, 1 mL of blood contains a few million white blood cells and a billion erythrocytes. The identification of CTCs, being in such low frequency, requires some special tumoral markers (e.g., EpCAM and cytokeratins) to capture and isolate them. Unfortunately, the common markers for recognizing the majority of CTCs are not effective enough for clinical application [ 41 ]. Although accumulated evidences have shown that the presence of CTCs is a strong negative prognostic factor in the patients with metastatic breast, lung and colorectal cancers, detecting CTCs might not be an ideal branch to hold on for the hope of early cancer detection [ 42 , 43 , 44 , 45 ].

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the circulatory system, which is mainly derived from the tumor cell death through necrosis and/or apoptosis [ 46 ]. Given its origin, ctDNA inherently carries cancer-specific genetic and epigenetic aberrations, which can be used as a surrogate source of tumor DNA for cancer diagnosis and prognostic prediction. Ideally, as a noninvasive tumor early screening tool, a liquid biopsy test should be able to detect many types of cancers and provide the information of tumor origin for further specific clinical management. In fact, the somatic mutations of ctDNA in different types of tumor are highly variable, even in the different individuals with the same type of tumor [ 47 ]. Additionally, most tumors do not possess driver mutations, with some notable exceptions, which make the somatic mutations of ctDNA not suitable for early detection of the tumor.

Increased methylation of the promoter regions of tumor suppressor genes is an early event in many types of tumor, suggesting that altered ctDNA methylation patterns could be one of the first detectable neoplastic changes associated with tumorigenesis [ 48 ]. ctDNA methylation profiling provides several advantages over somatic mutation analysis for cancer detection including higher clinical sensitivity and dynamic range, multiple detectable methylation target regions, and multiple altered CpG sites within each targeted genomic region. Further, each methylation marker is present in both cancer tissue and ctDNA, whereas only a fraction of mutations present in cancer tissue could be detected in ctDNA.

In 2017, there were two inspiring studies that revealed the values of using ctDNA methylation analysis for cancer early diagnosis [ 49 , 50 ]. After partitioning the human genome into blocks of tightly coupled CpG methylation sites, namely methylation haplotype blocks (MHBs), Guo and colleagues performed tissue-specific methylation analyses at the MHBs level to accurately determine the tissue origin of the cancer using ctDNA from their enrolled patients [ 49 ]. In another study, Xu and colleagues identified a hepatocellular carcinoma (HCC) enriched methylation marker panel by comparing the HCC tissue and blood leukocytes from normal individuals and showed that methylation profiles of HCC tumor DNA and matched plasma ctDNA were highly correlated. In this study, after quantitative measurement of the methylation level of candidate markers in ctDNA from a large cohort of 1098 HCC patients and 835 normal controls, ten methylation markers were selected to construct a diagnostic prediction model. The proposed model demonstrated a high diagnostic specificity and sensitivity, and was highly correlated with tumor burden, treatment response, and tumor stage [ 50 ].

With the rapid development of highly sensitive detection methods, especially the technologies of massively parallel sequencing or next-generation sequencing (NGS)-based assays and digital PCR (dPCR), we strongly believe that the identification of a broader “pan-cancer” methylation panel applied for ctDNA analyses, probably in combination with detections of somatic mutation and tumor-derived exosomes, would allow more effective screening for common cancers in the near future.

Edison Liu 1 , Hui-Yan Luo 2 .

[email protected]; [email protected]

Question 100: Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?

Though several anticancer agents are approved to treat different types of cancers, their full potentials have been limited due to the occurrence of drug resistance. Resistance to anticancer drugs develops by a variety of mechanisms, one of which is increased drug efflux by transporters. The ATP-binding cassette (ABC) family drug efflux transporter P-glycoprotein (P-gp or multi-drug resistance protein 1 [MDRP1]) has been extensively studied and is known to play a major role in the development of multi-drug resistance (MDR) to chemotherapy [ 51 ]. In brief, overexpressed P-gp efflux out a wide variety of anticancer agents (e.g.: vinca alkaloids, doxorubicin, paclitaxel, etc.), leading to a lower concentration of these drugs inside cancer cells, thereby resulting in MDR. Over the past three decades, researchers have developed several synthetic P-gp inhibitors to block the efflux of anticancer drugs and have tested them in clinical trials, in combination with chemotherapeutic drugs. But none were found to be suitable enough in overcoming MDR and to be released for marketing, mainly due to the side effects associated with cross-reactivity towards other ABC transporters (BCRP and MRP-1) and the inhibition of CYP450 drug metabolizing enzymes [ 52 , 53 ].

On the other hand, a number of phytochemicals have been reported to have P-gp inhibitory activity. Moreover, detailed structure–activity studies on these phytochemicals have delineated the functional groups essential for P-gp inhibition [ 53 , 54 ]. Currently, one of the phytochemicals, tetrandrine (CBT-1 ® ; NSC-77037), is being used in a Phase I clinical trial ( http://www.ClinicalTrials.gov ; NCT03002805) in combination with doxorubicin for the treatment of metastatic sarcoma. Before developing phytochemicals or their derivatives as P-gp inhibitors, they need to be investigated thoroughly for their cross-reactivity towards other ABC transporters and CYP450 inhibition, in order to avoid toxicities similar to the older generation P-gp inhibitors that have failed in clinical trials.

Therefore, the selectivity for P-gp over other drug transporters and drug metabolizing enzymes should be considered as important criterias for the development of phytochemicals and their derivatives for overcoming MDR.

Mohane Selvaraj Coumar and Safiulla Basha Syed.

Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.

[email protected]; [email protected]

Question 101: Is cell migration a selectable trait in the natural evolution of carcinoma?

The propensity of solid tumor malignancy to metastasize remains the main cause of cancer-related death, an extraordinary unmet clinical need, and an unanswered question in basic cancer research. While dissemination has been traditionally viewed as a late process in the progression of malignant tumors, amount of evidence indicates that it can occur early in the natural history of cancer, frequently when the primary lesion is still barely detectable.

A prerequisite for cancer dissemination is the acquisition of migratory/invasive properties. However, whether, and if so, how the migratory phenotype is selected for during the natural evolution of cancer and what advantage, if any, it may provide to the growing malignant cells remains an open issue. The answers to these questions are relevant not only for our understating of cancer biology but also for the strategies we adopt in an attempt of curbing this disease. Frequently, indeed, particularly in pharmaceutical settings, targeting migration has been considered much like trying “to shut the stable door after the horse has bolted” and no serious efforts in pursuing this aim has been done.

We argue, instead, that migration might be an intrinsic cancer trait that much like proliferation or increased survival confers to the growing tumor masses with striking selective advantages. The most compelling evidence in support for this contention stems from studies using mathematical modeling of cancer evolution. Surprisingly, these works highlighted the notion that cell migration is an intrinsic, selectable property of malignant cells, so intimately intertwined with more obvious evolutionarily-driven cancer traits to directly impact not only on the potential of malignant cells to disseminate but also on their growth dynamics, and ultimately provide a selective evolutionary advantage. Whether in real life this holds true remains to be assessed, nevertheless, work of this kind defines a framework where the acquisition of migration can be understood in a term of not just as a way to spread, but also to trigger the emergence of malignant clones with favorable genetic or epigenetic traits.

Alternatively, migratory phenotypes might emerge as a response to unfavorable conditions, including the mechanically challenging environment which tumors, and particularly epithelial-derived carcinoma, invariably experience. Becoming motile, however, may not per se being fixed as phenotypic advantageous traits unless it is accompanied or is causing the emergence of specific traits, including drug resistance, self-renewal, and survival. This might be the case, for example, during the process of epithelial-to-mesenchymal transition (EMT), which is emerging as an overarching mechanism for dissemination. EMT, indeed, may transiently equip individual cancer cells not only with migratory/invasive capacity but also with increased resistance to drug treatment, stemness potential at the expanse of fast proliferation.

Thus, within this framework targeting pro-migratory genes, proteins and processes may become a therapeutically valid alternative or a complementary strategy not only to control carcinoma dissemination but also its progression and development.

Giorgio Scita.

IFOM, The FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), School of Medicine, University of Milan, Via Festa del Perdono 7, 20122, Italy.

[email protected]

Qian CN, Zhang W, Xu RH. Defeating cancer: the 150 most important questions in cancer research and clinical oncology. Chin J Cancer. 2016;35(1):104. https://doi.org/10.1186/s40880-016-0165-4 .

Article   PubMed   PubMed Central   Google Scholar  

Wee JT, Poh SS. The most important questions in cancer research and clinical oncology: question 1. Could the vertical transmission of human papilloma virus (HPV) infection account for the cause, characteristics, and epidemiology of HPV-positive oropharyngeal carcinoma, non-smoking East Asian female lung adenocarcinoma, and/or East Asian triple-negative breast carcinoma? Chin J Cancer. 2017;36(1):13. https://doi.org/10.1186/s40880-016-0168-1 .

Venniyoor A. The most important questions in cancer research and clinical oncology—Question 2–5. Obesity-related cancers: more questions than answers. Chin J Cancer. 2017;36(1):18. https://doi.org/10.1186/s40880-017-0185-8 .

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 6–14: Edited by Chinese Journal of Cancer. Chin J Cancer. 2017;36(1):33. https://doi.org/10.1186/s40880-017-0200-0 .

Article   Google Scholar  

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 15–24: Edited by Chinese Journal of Cancer. Chin J Cancer. 2017;36(1):39. https://doi.org/10.1186/s40880-017-0205-8 .

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 25–30: Edited by Chinese Journal of Cancer. Chin J Cancer. 2017;36(1):42. https://doi.org/10.1186/s40880-017-0210-y .

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 31–39: Edited by Chinese Journal of Cancer. Chin J Cancer. 2017;36(1):48. https://doi.org/10.1186/s40880-017-0215-6 .

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 40–49. Chin J Cancer. 2017;36(1):55. https://doi.org/10.1186/s40880-017-0222-7 .

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 50–56. Chin J Cancer. 2017;36(1):69. https://doi.org/10.1186/s40880-017-0236-1 .

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 57–66: Edited by Chinese Journal of Cancer. Chin J Cancer. 2017;36(1):79. https://doi.org/10.1186/s40880-017-0249-9 .

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 67–75: Edited by Chinese Journal of Cancer. Chin J Cancer. 2017;36(1):86. https://doi.org/10.1186/s40880-017-0254-z .

Editorial Office of Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 76–85: Edited by Chinese Journal of Cancer. Chin J Cancer. 2017;36(1):91. https://doi.org/10.1186/s40880-017-0259-7 .

Chinese Journal of C. The 150 most important questions in cancer research and clinical oncology series: questions 86–93: Edited by Chinese Journal of Cancer. Chin J Cancer. 2018;37(1):1. https://doi.org/10.1186/s40880-018-0266-3 .

Weinberg RA. Coming full circle-from endless complexity to simplicity and back again. Cell. 2014;157(1):267–71. https://doi.org/10.1016/j.cell.2014.03.004 .

Article   CAS   PubMed   Google Scholar  

Niu N, Mercado-Uribe I, Liu J. Dedifferentiation into blastomere-like cancer stem cells via formation of polyploid giant cancer cells. Oncogene. 2017;36(34):4887–900. https://doi.org/10.1038/onc.2017.72 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Niu N, Zhang J, Zhang N, Mercado-Uribe I, Tao F, Han Z, et al. Linking genomic reorganization to tumor initiation via the giant cell cycle. Oncogenesis. 2016;5(12):e281. https://doi.org/10.1038/oncsis.2016.75 .

Zhang S, Mercado-Uribe I, Xing Z, Sun B, Kuang J, Liu J. Generation of cancer stem-like cells through the formation of polyploid giant cancer cells. Oncogene. 2014;33(1):116–28. https://doi.org/10.1038/onc.2013.96 .

Hemberger M, Dean W, Reik W. Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington’s canal. Nat Rev Mol Cell Biol. 2009;10(8):526–37. https://doi.org/10.1038/nrm2727 .

Liu J. The dualistic origin of human tumors. Semin Cancer Biol. 2018. https://doi.org/10.1016/j.semcancer.2018.07.004 .

Zhou B, Xu JW, Cheng YG, Gao JY, Hu SY, Wang L, et al. Early detection of pancreatic cancer: where are we now and where are we going? Int J Cancer. 2017;141(2):231–41. https://doi.org/10.1002/ijc.30670 .

Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467(7319):1114–7. https://doi.org/10.1038/nature09515 .

Sharma R, Huang X, Brekken RA, Schroit AJ. Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies. Br J Cancer. 2017;117(4):545–52. https://doi.org/10.1038/bjc.2017.183 .

Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371(11):1039–49. https://doi.org/10.1056/NEJMra1404198 .

Takada T, Yasuda H, Amano H, Yoshida M, Uchida T. Simultaneous hepatic resection with pancreato-duodenectomy for metastatic pancreatic head carcinoma: does it improve survival? Hepatogastroenterology. 1997;44(14):567–73.

CAS   PubMed   Google Scholar  

Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47–52. https://doi.org/10.1038/nature16965 .

Frigerio I, Regi P, Giardino A, Scopelliti F, Girelli R, Bassi C, et al. Downstaging in stage IV pancreatic cancer: a new population eligible for surgery? Ann Surg Oncol. 2017;24(8):2397–403. https://doi.org/10.1245/s10434-017-5885-4 .

Article   PubMed   Google Scholar  

Van Laethem JL, Riess H, Jassem J, Haas M, Martens UM, Weekes C, et al. Phase I/II study of refametinib (BAY 86-9766) in combination with gemcitabine in advanced pancreatic cancer. Target Oncol. 2017;12(1):97–109. https://doi.org/10.1007/s11523-016-0469-y .

Jiang H, Hegde S, Knolhoff BL, Zhu Y, Herndon JM, Meyer MA, et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med. 2016;22(8):851–60. https://doi.org/10.1038/nm.4123 .

Mace TA, Shakya R, Pitarresi JR, Swanson B, McQuinn CW, Loftus S, et al. IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer. Gut. 2018;67(2):320–32. https://doi.org/10.1136/gutjnl-2016-311585 .

Immunotherapy Beats Chemo for Bladder Cancer. Cancer Discov. 2017;7(5):OF8. https://doi.org/10.1158/2159-8290.cd-nb2017-035 .

Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):603–15. https://doi.org/10.1016/S1470-2045(18)30142-6 .

Garassino MC, Cho BC, Kim JH, Mazieres J, Vansteenkiste J, Lena H, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018;19(4):521–36. https://doi.org/10.1016/S1470-2045(18)30144-X .

U.S. National Library of Medicine. ClinicalTrials.gov.

Liu Z, Yokoyama NN, Blair CA, Li X, Avizonis D, Wu XR, et al. High sensitivity of an Ha-RAS transgenic model of superficial bladder cancer to metformin is associated with approximately 240-fold higher drug concentration in urine than serum. Mol Cancer Ther. 2016;15(3):430–8. https://doi.org/10.1158/1535-7163.MCT-15-0714-T .

Menendez JA, Quirantes-Pine R, Rodriguez-Gallego E, Cufi S, Corominas-Faja B, Cuyas E, et al. Oncobiguanides: paracelsus’ law and nonconventional routes for administering diabetobiguanides for cancer treatment. Oncotarget. 2014;5(9):2344–8. https://doi.org/10.18632/oncotarget.1965 .

Peng M, Su Q, Zeng Q, Li L, Liu Z, Xue L, et al. High efficacy of intravesical treatment of metformin on bladder cancer in preclinical model. Oncotarget. 2016;7(8):9102–17. https://doi.org/10.18632/oncotarget.6933 .

Peng M, Huang Y, Tao T, Peng CY, Su Q, Xu W, et al. Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk. Sci Rep. 2016;6:28611. https://doi.org/10.1038/srep28611 .

Definition of liquid biopsy. In: NCI Dictionary of Cancer Terms. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/liquid-biopsy .

Ta A. A case of cancer in which cells similar to those in the tumors were seen in the blood after death. Aust Med J. 1869;14:146–9.

Google Scholar  

Miller MC, Doyle GV, Terstappen LW. Significance of circulating tumor cells detected by the cell search system in patients with metastatic breast colorectal and prostate cancer. J Oncol. 2010;2010:617421. https://doi.org/10.1155/2010/617421 .

Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450(7173):1235–9. https://doi.org/10.1038/nature06385 .

Bidard FC, Proudhon C, Pierga JY. Circulating tumor cells in breast cancer. Mol Oncol. 2016;10(3):418–30. https://doi.org/10.1016/j.molonc.2016.01.001 .

Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21. https://doi.org/10.1200/JCO.2007.15.8923 .

Ignatiadis M, Dawson SJ. Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality? Ann Oncol. 2014;25(12):2304–13. https://doi.org/10.1093/annonc/mdu480 .

Krebs MG, Sloane R, Priest L, Lancashire L, Hou JM, Greystoke A, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol. 2011;29(12):1556–63. https://doi.org/10.1200/JCO.2010.28.7045 .

Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579–86. https://doi.org/10.1200/JCO.2012.45.2011 .

Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9. https://doi.org/10.1038/nature12634 .

Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358(11):1148–59. https://doi.org/10.1056/NEJMra072067 .

Guo S, Diep D, Plongthongkum N, Fung HL, Zhang K, Zhang K. Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA. Nat Genet. 2017;49(4):635–42. https://doi.org/10.1038/ng.3805 .

Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater. 2017;16(11):1155–61. https://doi.org/10.1038/nmat4997 .

Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer. 2018. https://doi.org/10.1038/s41568-018-0005-8 .

Chung FS, Santiago JS, Jesus MF, Trinidad CV, See MF. Disrupting P-glycoprotein function in clinical settings: what can we learn from the fundamental aspects of this transporter? Am J Cancer Res. 2016;6(8):1583–98.

CAS   PubMed   PubMed Central   Google Scholar  

Syed SB, Coumar MS. P-Glycoprotein mediated multidrug resistance reversal by phytochemicals: a review of SAR & future perspective for drug design. Curr Top Med Chem. 2016;16(22):2484–508.

Abdallah HM, Al-Abd AM, El-Dine RS, El-Halawany AM. P-Glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: a review. J Adv Res. 2015;6(1):45–62. https://doi.org/10.1016/j.jare.2014.11.008 .

Download references

Author information

Authors and affiliations, rights and permissions.

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Cite this article.

Cancer Communications. The 150 most important questions in cancer research and clinical oncology series: questions 94–101. Cancer Commun 38 , 69 (2018). https://doi.org/10.1186/s40880-018-0341-9

Download citation

Received : 13 November 2018

Accepted : 19 November 2018

Published : 26 November 2018

DOI : https://doi.org/10.1186/s40880-018-0341-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Tumor origin
• Polyploid giant cancer cell
• Pancreatic ductal adenocarcinoma
• Liquid biopsy
• Spontaneous animal model
• Chemotherapy
• Immunotherapy
• Precision treatment
• Vaccine immunization
• Circulating tumor cell
• Circulating tumor DNA
• CpG methylation
• Methylation haplotype block
• Phytochemicals
• P-Glycoprotein
• Multi-drug resistance
• P-Glycoprotein inhibitor
• Epithelial-to-mesenchymal transition
• Pro-migratory gene

ISSN: 2523-3548

• General enquiries: [email protected]

• Theses & Dissertations
• Organizational Chart
• Epi EDI Committee
• Strategic Plan
• Master of Public Health
• Master of Science
• Doctor of Philosophy
• Concurrent Degrees
• Graduate Certificates
• MPH Eligibility and Application Requirements
• MS Eligibility and Application Requirements
• PhD Eligibility and Application Requirements
• Non-Matriculated Applicants
• Student Life
• Undergraduate Course Listings
• Graduate Course Listings
• Registration FAQs
• Technology Requirements
• Student Opportunities
• Epi Student Spaces
• Student Canvas Site
• Research Areas
• Centers & Research Units
• Partnerships
• Our Graduates
• Stay Connected
• Make a Gift
• In the News
• Epi Stories
• Epi Seminar
• Opportunities
• Epi Newsletters Submission Guide
• Curriculum Resources
• Faculty Resources
• Fiscal Resources
• Reimbursement Form
• Health and Safety Resources
• IT Resources
• Working at HRC
• Equipment Inventory Policy
• Staff Resources

Filter Theses/Dissertations:

Sph soulcatcher, connect with us:.

© 2024 University of Washington | Seattle, WA

A COMPREHENSIVE ANALYSIS OF CANCER-RELATED FATIGUE IN EARLY BREAST CANCER SURVIVORS: A COMMUNITY-BASED EXERCISE PERSPECTIVE

Add to collection, downloadable content.

• Affiliation: College of Arts and Sciences, Department of Exercise and Sport Science
• PURPOSE: The purpose of this investigation was to gain a better overall understanding of cancer-related fatigue (CRF) in early-breast cancer survivors (EBCS) within a community-based exercise setting by evaluating baseline CRF severity, CRF change after exercise, and identifying potential correlates of CRF. PARTICIPANTS: 33 EBCS (54  11 years) within one year of completing primary chemotherapy or radiation and 21 sedentary age-matched controls (CON) (54  8 years) were enrolled. METHODS: Pre/post intervention measurements for each group included the PROMIS Fatigue 7a, cardiorespiratory fitness (VO2peak), lower/upper body strength, quality of life, depression/anxiety, pain, sleep quality, self-efficacy for fatigue management, physical function, and self-reported physical activity/outcome exercise expectations. Both groups participated in a 16-week aerobic/resistance exercise intervention, exercising under supervision 3 days/week for 1 hour each day. Exercise adherence and compliance was tracked. RESULTS: At baseline, CRF scores were not statistically different between groups (EBCS: 16.9  5.75; CON: 14.2  3.4, p=0.121). Lower CRF in EBCS was associated with better quality of life (adj R2 = 0.447; p<0.001), mental health (adj R2 = 0.414; p<0.001), outcome expectations for exercise (adj R2 = 0.208; p<0.001), and less depression (adj R2 = 0.360; p<0.001) at baseline. Post-exercise, CRF improved in EBCS (-2.6, Cohen’s D = 0.51) but not in CON (0.0, Cohen’s D = 0.02). Post-exercise, improved CRF in EBCS was also associated with better overall self-reported quality of life (adj R2 = 0.364; p<0.001), less depression (adj R2 = 0.223; p<0.01), higher self-efficacy for fatigue self-management (adj R2 = 0.433; p<0.01), higher outcome expectations for exercise (adj R2 = 0.227; p<0.01), and better balance (adj R2 = 0.136; p<0.05). CONCLUSIONS: EBCS enrolled in community-based exercise programs report mild fatigue levels at baseline that are similar to CON. Despite this similarity, EBCS’ fatigue was significantly associated with multiple psychosocial outcomes at baseline whereas CON was not. Community-based exercise is beneficial for alleviating CRF in EBCS, with improvements primarily associated with psychosocial and functional outcomes. Further research in larger samples is needed to validate the impact of community-based exercise for CRF management in EBCS and to identify potential moderators of the association.
• Kinesiology
• https://doi.org/10.17615/eb1f-6z43
• Dissertation
• In Copyright - Educational Use Permitted
• Battaglini, Claudio L
• Hanson, Erik D
• Kerr, Zachary Y
• Nyrop, Kirsten A
• Muss, Hyman B
• Doctor of Philosophy
• University of North Carolina at Chapel Hill Graduate School

This work has no parents.

Select type of work

Master's papers.

Deposit your masters paper, project or other capstone work. Theses will be sent to the CDR automatically via ProQuest and do not need to be deposited.

Scholarly Articles and Book Chapters

Deposit a peer-reviewed article or book chapter. If you would like to deposit a poster, presentation, conference paper or white paper, use the “Scholarly Works” deposit form.

Undergraduate Honors Theses

Deposit your senior honors thesis.

Scholarly Journal, Newsletter or Book

Deposit a complete issue of a scholarly journal, newsletter or book. If you would like to deposit an article or book chapter, use the “Scholarly Articles and Book Chapters” deposit option.

Deposit your dataset. Datasets may be associated with an article or deposited separately.

Deposit your 3D objects, audio, images or video.

Poster, Presentation, Protocol or Paper

Deposit scholarly works such as posters, presentations, research protocols, conference papers or white papers. If you would like to deposit a peer-reviewed article or book chapter, use the “Scholarly Articles and Book Chapters” deposit option.

Thesis: Surviving Cervical Cancer: A History of Prevention, Early Detection, and Treatment

Editor's note:

Alexis Darby defended her thesis titled “Surviving Cervical Cancer: A History of Prevention, Early Detection, and Treatment,” in May 2019 in front of committee members Jane Maienschein, Carolina Abboud, and Karin Ellison, earning her a Bachelor’s degree from Barrett, the Honors College. https://repository.asu.edu/items/53339

Cervical cancer, which many physicians as of 2019 consider to be a success in terms of establishing widely used forms of early preventative and diagnostic technologies, experienced a reduction in incidence rates in women by over fifty percent between 1975 and 2016. Cervical cancer does not often present in women with symptoms until it has entered a later stage of the disease. Because of this fact, in the early twentieth century, physicians were often only able to diagnose cervical cancer when either the woman reported complaints or there was a visual confirmation of lesions on the cervix. The symptoms women often reported included vague abdominal pain, bleeding after sex, and abnormal amounts of vaginal discharge, all of which are non-specific symptoms, making it even harder for women to be diagnosed with cervical cancer.

This thesis answers the following question: How does the history of cervical cancer show that prevention helps reduce rates of cancer-related deaths among women? By studying the history of cervical cancer, people can understand how a cancer that was once one of the top killers of women in the US has declined to become one of the lowest through the establishment of and effective communication of early prevention and diagnostics, both among the general public and within the medical community itself. This thesis is organized based on key episodes which were pertinent to the history of cervical cancer, primarily within the United States and Europe. The episodes are organized in context of the shifts in thought regarding cervical cancer and include topics such as vaccine technologies like the Gardasil and Cervarix vaccines, social awareness movements that educated women on the importance of early detection, and analyses of the early preventative strategies and attempts at treating cervical cancer.

After analyzing eleven key episodes, the thesis determined that, through the narrative of early attempts to treat cervical cancer, shifting the societal thought on cancer, evolving the importance of early detection, and, finally, obtaining a means of prevention, the history of cervical cancer does demonstrate that the development of preventative strategies has resulted in reducing cancer-related deaths among women. Understanding what it took for physicians to evolve from simply detecting cervical cancer to being able to prevent it entirely matters because it can change the way we think about managing other forms of cancer.

How to cite

Last modified, share this page.

Cancer – an overview

• PMID: 29952494

Cancer is characterized by proliferation of cells that have managed to evade central endogenous control mechanisms. Cancers are grouped according to their organ or tissue of origin, but increasingly also based on molecular characteristics of the respective cancer cells. Due to the rapid technological advances of the last years, it is now possible to analyze the molecular makeup of different cancer types in detail within short time periods. The accumulating knowledge about development and progression of cancer can be used to develop more precise diagnostics and more effective and/or less toxic cancer therapies. In the long run, the goal is to offer to every cancer patient a therapeutic regimen that is tailored to his individual disease and situation in an optimal way.

Publication types

• Antineoplastic Agents / therapeutic use*
• Drug Resistance, Neoplasm
• Neoplasms / drug therapy*
• Neoplasms / pathology
• Precision Medicine
• Antineoplastic Agents

• Open access
• Published: 15 April 2024

Associations between cardiovascular diseases and cancer mortality: insights from a retrospective cohort analysis of NHANES data

• Chenliang Ge 1 ,
• Zhiyuan Jiang 1 ,
• Binghua Long 1 ,
• Qingjian Lu 1 &

BMC Public Health volume  24 , Article number:  1049 ( 2024 ) Cite this article

364 Accesses

Metrics details

This study explored the association of cardiovascular disease (CVD) with cancer mortality risk in individuals with or without a history of cancer, to better understand the interplay between CVD and cancer outcomes.

Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, a retrospective cohort analysis was conducted. This analysis accounted for the survey’s complex design to ensure national representativeness. The association of CVD with cancer mortality was assessed through multivariable Cox proportional hazards models.

The present study included 59,653 participants, of whom 54,095 did not have cancer and 5558 had a history of cancer. In individuals without cancer, heart failure (HF) was associated with an increased risk of mortality from cancer (HR, 1.36; 95% CI, 1.09–1.69; P  = 0.005). In participants with cancer, HF correlated with a higher risk of mortality from cancer (HR, 1.76; 95% CI, 1.32–2.34; P  < 0.001). Diabetes (DM), hypertension (HBP) and coronary heart disease (CHD) were not significantly associated with an increased risk of mortality from cancer. Significant differences were observed in the interaction between cancer and CHD (HR, 0.68; 95% CI, 0.53–0.87; P  = 0.002). For cancer and HBP, a similar trend was noted (HR, 0.75; 95% CI, 0.62–0.91; P  = 0.003). No significant differences were found in interactions between HF, DM and cancer.

Conclusions

HF was associated with an increased risk of mortality from cancer, regardless of cancer history, while HBP, CHD and DM showed no significant association. These findings underscore the importance of understanding the mechanisms behind the increased risk of cancer mortality following HF.

Peer Review reports

Cancer and cardiovascular disease (CVD) are the leading non-communicable causes of global morbidity and mortality. In 2015, CVD resulted in 17.7 million deaths globally, while cancer was responsible for 8.8 million deaths [ 1 , 2 , 3 ]. Since the 1990s, there has been a notable decline in cancer-related mortality, with projections indicating that the number of cancer survivors in the United States will exceed 26 million by 2040 [ 4 , 5 , 6 , 7 ]. This growing population of cancer survivors faces an increased risk of developing CVD, with cardiac risk factors significantly influencing treatment-related cardiotoxicity. Both CVD and cancer share common risk factors, such as obesity and diabetes (DM), suggesting a potential shared pathobiology—a concept supported by emerging evidence [ 8 , 9 ]. This intersection of cancer and CVD has led to the development of the specialized field of cardio-oncology [ 10 , 11 , 12 ].

Despite the recognized link between cancer and CVD, the evidence guiding clinical decisions in cardio-oncology remains sparse. Extensive research has been conducted on cancer treatment-induced cardiotoxicity, the impact of pre-existing CVD on cancer mortality, especially among cancer patients, is less understood [ 13 , 14 , 15 ]. Recognizing this gap, our study seeks to provide empirical evidence on the role of CVD in cancer mortality, utilizing data from the National Health and Nutrition Examination Survey (NHANES). We hypothesize that CVD significantly increases the risk of cancer mortality and aimed to exam the association between CVD and cancer mortality in individuals with or without a history of cancer.

Study population

This study utilized data from the NHANES, a representative, multistage, and stratified health survey conducted in the United States [ 16 , 17 , 18 , 19 , 20 ]. This study received ethical approval from the National Center for Health Statistics (NCHS) Institutional Review Board and informed consent was obtained from all participants. The research adhered to the Tenets of the Declaration of Helsinki. Ethical considerations have been rigorously followed to ensure that participants confidentiality was not impacted. We included participants from the NHANES database spanning 1999 to 2018, exclusion criteria were set to omit individuals without clear cancer status or those missing follow-up survival data. Participants were categorized into cancer and non-cancer groups based on physician-reported cancer diagnoses (Fig.  1 ). NCHS linked the survey data with death certificate records from the National Death Index (NDI) for mortality follow-up. Follow-up time was calculated in person-months from the interview date to either the date of death, the end of the mortality follow-up period, or December 31, 2019, whichever occurred first. The linked mortality files classified causes of death into nine categories using (ICD)-10 codes. Our primary focus was on deaths due to malignant neoplasms (ICD-10 codes: C00-C97) and all-cause mortality.

Flow diagram of study sample selection

Sociodemographic characteristics and covariates

Participants provided information on age, gender, race and ethnic group (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Other Race), education level (< High school, High school, some college or Associates degree, College graduate) and marital status (never married, married or living with a partner, separated or divorced or widowed). The ratio of family income to the poverty level was categorized as < 1, 1 to 3, or > 3. Smoking status was categorized as current, past or never. Body mass index (BMI), calculated as the weight in kilograms divided by the square of the height in meters, was classified into three weight-status groups: normal (BMI < 25), overweight (BMI 25  ∼  30), or obese (BMI ≥ 30). Creatinine data were obtained from the original database. The presence of various comorbidities, such as DM, hypertension (HBP), coronary heart disease (CHD), heart failure (HF), stroke, chronic bronchitis and chronic liver disease, was determined based on reported diagnoses from a physician.

Statistical analysis

We employed complex survey design adjustments from NHANES data to ensure representative estimates for the US population, accounting for sample weights, clustering, and stratification [ 21 , 22 ]. Data analysis was conducted using R software version 4.3.1. Categorical variables were analyzed using Rao-Scott adjusted Chi-square test and continuous variables were analyzed using weighted mean comparisons. Kaplan-Meier survival curves provided weighted comparisons of the cumulative incidence of cancer-related deaths and all-cause deaths. We rigorously tested the proportional hazards assumption through the examination of martingale residuals and the application of time-dependent covariate tests. Cox proportional hazards models, incorporating survey sample weights, were utilized to estimate hazard ratio (HR) for cancer mortality, adjusting for potential confounders including gender, age, BMI, race, education, marital status, income level and CVD conditions including CHD, HF, HBP, DM. Missing data were addressed using the fully efficient fractional imputation technique, with less than 3% missing values for most variables, except for BMI (6.3% missing), family income-to-poverty ratio (9.9% missing) and Creatinine (11.8% missing) [ 23 ]. Sensitivity analyses excluded subjects with missing values in BMI, marital status, creatinine, and DM, HBP, CHD, HF statuses. Statistical significance was set at p  ≤ 0.05.

Participants characteristics

The study cohort comprised 59,653 individuals who were categorized into the non-cancer group ( N  = 54,095) and the cancer group ( N  = 5558). Table  1 presents the clinical characteristics of non-cancer and cancer participants. Compared to non-cancer participants, those with cancer were older, had a higher proportion of females, and exhibited elevated systolic blood pressure levels. Diastolic blood pressure levels were lower in the cancer group. A lower percentage of smokers was noted in the cancer group, and this group had a shorter follow-up time. In terms of education level, individuals with or above a college education were more prevalent in the cancer group, while those with an education level below high school were less frequent in the cancer group. The proportion of participants living alone was notably higher in the cancer group. Creatinine levels were higher in cancer participants than in non-cancer participants. Cancer participants, in comparison with non-cancer participants, were significantly more likely to have DM (15.5% vs. 8.2%, respectively; P  < 0.001), HBP (50.4% vs. 28.3%, respectively; P  < 0.001), HF (6.2% vs. 2.0%, respectively; P  < 0.001), CHD (8.1% vs. 3.0%, respectively; P  < 0.001), Stroke (6.5% vs. 2.4%, respectively; P  < 0.001), Chronic bronchitis (11.2% vs. 5.6%, respectively; P  < 0.001) and Liver condition (5.3% vs. 3.3%, respectively; P  < 0.001). Among all cancer participants, skin cancer had the highest proportion, accounting for 28.3%, followed by breast cancer (15.8%), prostate cancer (9.4%), cervix cancer (8.1%), melanoma (7.4%), colon cancer (4.7%), uterus cancer (3.6%), lung cancer (2.2%), other types of cancer accounting for 20.5%.

Association of CVD with cancer mortality

Examination of martingale residuals showed the proportional hazards assumption is reasonable for data of the present study (Supplemental figure). Among all participants, presence of cancer was associated with higher risk of cancer mortality among cancer participants, when compared with participants without cancer (HR 2.35, 95%CI 2.14  ∼  2.58, P  < 0.001). Presence of HF was associated with higher risk of cancer mortality among all participants, when compared with participants without HF (HR 1.52, 95%CI 1.34  ∼  1.71, P  < 0.001). DM, HBP, CHD were not associated with significant increased cancer mortality risk. There was statistically significant difference in the associations of cancer× CHD interaction (HR 0.68, 95%CI 0.53  ∼  0.87, P  = 0.002) and cancer× HBP interaction (HR 0.75, 95%CI 0.62  ∼  0.91, P  = 0.003). There was no statistically significant difference in the associations of cancer× HF interaction ( P  = 0.891) and cancer× DM interaction ( P  = 0.56) (Table  2 ).

Among non-cancer participants, presence of HF was associated with higher risk of cancer mortality among cancer participants, when compared with participants without HF (HR 1.36, 95%CI 1.09  ∼  1.69, P  = 0.005). DM, HBP, CHD were not associated with significant increased cancer mortality risk. Among cancer participants, presence of HF was associated with higher risk of cancer mortality among cancer participants, when compared with participants without HF (HR 1.76, 95%CI 1.32  ∼  2.34, P  < 0.001). DM, HBP, CHD were not associated with significant increased cancer mortality risk (Table  3 ).

Kaplan-Meier curves showed cumulative all-cause mortality and cancer mortality. Cancer participants with HF had a higher all-cause mortality compared with cancer participants without HF. Cancer participants with HF also had a higher cancer mortality compared with cancer participants without HF. Non-cancer participants with HF had a higher all-cause mortality compared with non-cancer participants without HF. Non-cancer participants with HF also had a higher cancer mortality compared with non-cancer participants without HF (Fig.  2 ).

Kaplan-Meier Survival Curves for All-Cause and cancer Mortality. Cumulative mortality rates were estimated with use of imputation-adjusted survey weights. ( A ) All-cause mortality among cancer participants with heart failure (HF) versus those without. ( B ) Cancer mortality among cancer participants with HF versus those without. ( C ) All-cause mortality among non-cancer participants with HF versus those without. ( D ) Cancer mortality among non-cancer participants with HF versus those without. Mortality rates are adjusted for imputation and survey weights to reflect the NHANES cohort accurately

In sensitivity analyses, presence of HF was associated with higher risk of cancer mortality among all participants, when compared with participants without HF (HR 1.56, 95%CI 1.18  ∼  2.06, P  < 0.001). DM, HBP, CHD were not associated with significant increased cancer mortality risk. Among non-cancer participants, presence of HF was associated with higher risk of cancer mortality among cancer participants, when compared with participants without HF (HR 1.47, 95%CI 1.02  ∼  2.13, P  = 0.03). Among cancer participants, presence of HF was associated with higher risk of cancer mortality among cancer participants, when compared with participants without HF (HR 1.69, 95%CI 1.03  ∼  2.79, P  = 0.037).

The present study embarked on an exploration of the associations between CVD and cancer mortality, leveraging a comprehensive retrospective cohort analysis of data from NHANES spanning 1999 to 2018. Confirming our hypotheses, we found that HF was associated with a 37% increased risk of cancer mortality in participants without cancer and a 73% increase in those with cancer, compared to those without HF. The findings of this investigation revealed that HF is a notable predictor of increased cancer mortality risk irrespective of cancer history, a discovery that underscores the intricate and potentially bidirectional relationship between HF and cancer. Conversely, DM, HBP, and CHD did not exhibit a statistically significant association with cancer mortality, highlighting the unique position of HF within the spectrum of CVD affecting cancer outcomes.

Our findings concur with prior research that has indicated a heightened cancer risk associated with HF [ 24 , 25 , 26 , 27 ] and may be linked to shared risk factors, such as the association of chronic kidney disease with increased cancer risk in the elderly [ 28 ]. We observed that common risk factors like HBP, obesity, DM, and tobacco use are shared between cancer and heart failure. Similarly, Symptoms such as fatigue, dyspnea, and weight loss also present in both HF and cancer, adding complexity to their management [ 29 , 30 , 31 , 32 ]. Koene et al. elucidated the shared risk factors and biological mechanisms between CVD and cancer, suggesting a unified pathobiological framework that may contribute to the co-occurrence of these diseases [ 9 ]. Chronic inflammation and immune modulation in HF could promote tumor progression. Experimental models have shown a causal relationship between ischemic HF and tumor growth, possibly mediated by factors released from failing myocardium [ 8 , 33 , 34 , 35 , 36 , 37 ]. Sympathetic nervous system activation in HF, as observed in breast cancer mouse models, is associated with increased metastasis, which can be mitigated by beta-blocker therapy [ 38 ]. This suggests a potential therapeutic role for beta-blockers in cancer patients with elevated heart rates [ 39 ].

Our study uniquely identified that CHD and HBP demonstrated an interactive effect with cancer, which may provide a protective influence. This interaction may be linked to the protective effects of medications used in the treatment of HBP and CHD. Angiotensin Receptor Blocker (ARB) hold anti-tumor potential by inhibiting the action of angiotensin II, as do Angiotensin-Converting Enzyme Inhibitors (ACEI), which block the generation of angiotensin II and are considered to have anti-tumor effects. Long-term ARB and ACEI use was significantly associated with a reduced risk of incident cancer [ 40 ]. Statins, such as atorvastatin, simvastatin, rosuvastatin and pravastatin, have demonstrated anticancer activity across various cancer types in laboratory studies. These drugs exert direct effects on cancer cells, influencing tumor initiation, progression, metastasis, and response to therapy. While the role of statins in cancer prevention is debated, robust research confirms their potential as repurposed drugs in the fight against cancer. Recent systematic reviews and meta-analyses indicate that statin treatment is linked to a decreased risk of overall mortality and cancer-specific mortality in advanced-stage cancer patients. The multifaceted effects of statins, including antiproliferative and apoptotic-inducing properties, position them as promising agents in cancer therapy, introducing innovative perspectives and novel treatment targets [ 41 , 42 , 43 , 44 , 45 ].

Our study, while providing valuable insights into the association between CVD and cancer mortality, is subject to several limitations. Firstly, relying on data from NHANES introduces potential biases such as recall bias and inaccuracies in self-reported health and lifestyle factors. The retrospective cohort design, though robust, cannot establish causality between CVD conditions and cancer mortality, highlighting the need for prospective or randomized controlled designs in future research. Despite adjusting for multiple confounders, residual or unmeasured confounding factors could still influence the observed associations. The study primarily focuses on HF, DM, HBP and CHD, with limited data on other CVD conditions and specific types of cancer, which constrains our understanding of these associations. Additionally, the span of data from 1999 to 2018 encompasses significant changes in healthcare and lifestyle, the implications of which may not be fully captured in our analysis. Addressing these limitations in future studies is crucial for refining our understanding of the complex interplay between cardiovascular health and cancer outcomes.

In conclusion, we found that HF exhibited an elevated risk of cancer mortality, irrespective of a patient’s cancer history. This association underscores the importance of integrating cardiovascular health management into cancer care strategies. Conversely, DM, HBP and CHD did not demonstrate a significant correlation with increased cancer mortality risk, highlighting the specificity of HF ‘s impact on cancer outcomes. Our findings contribute to the burgeoning field of cardio-oncology, emphasizing the need for a multidisciplinary approach to patient care that addresses both cardiovascular health and cancer risk. The nuanced understanding of the relationship between specific cardiovascular conditions and cancer mortality could lead to more effective prevention, management, and treatment strategies that holistically address patient health. As the interplay between CVD and cancer continues to reveal its complexity, ongoing research in this intersection is imperative for advancing patient care and improving outcomes.

Data availability

The data and the simulation results that support the findings of this study are available in Figshare with the identifie. All National Health and Nutrition Examination Survey data were accessed from https://www.cdc.gov/nchs/nhanes.htm .

Abbreviations

• Cardiovascular disease

National Health and Nutrition Examination Survey

• Heart failure

Hypertension

Coronary heart disease

National Center for Health Statistics

National Death Index

International Classification of Diseases

Body mass index

Angiotensin Receptor Blocker

Angiotensin-Converting Enzyme Inhibitors

WHO. Cardiovascular diseases. http://www.hoint/mediacentre/factsheets/fs317/en/ (18 October 2019).

Cancer W. October: http://www.who.int/mediacentre/factsheets/fs297/en / (18 2019).

Murphy SL, Xu J, Kochanek KD, Curtin SC, Arias E. Deaths: final data for 2015. National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics. Natl Vital Stat Syst. 2017;66(6):1–75.

Google Scholar  

Herrmann J, Lerman A, Sandhu NP, Villarraga HR, Mulvagh SL, Kohli M. Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Clinic proceedings 2014;89(9):1287–1306.

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71(3):209–49.

Article   Google Scholar  

Coleman MP, Gatta G, Verdecchia A, Estève J, Sant M, Storm H, Allemani C, Ciccolallo L, Santaquilani M, Berrino F. EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century. Annals Oncology: Official J Eur Soc Med Oncol. 2003;14(Suppl 5):v128–149.

Bluethmann SM, Mariotto AB, Rowland JH. Anticipating the silver tsunami: prevalence trajectories and Comorbidity Burden among Older Cancer survivors in the United States. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research. Cosponsored Am Soc Prev Oncol. 2016;25(7):1029–36.

de Boer RA, Meijers WC, van der Meer P, van Veldhuisen DJ. Cancer and heart disease: associations and relations. Eur J Heart Fail. 2019;21(12):1515–25.

Article   PubMed   Google Scholar  

Koene RJ, Prizment AE, Blaes A, Konety SH. Shared Risk factors in Cardiovascular Disease and Cancer. Circulation. 2016;133(11):1104–14.

Article   PubMed   PubMed Central   Google Scholar  

Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, Boriani G, Cardinale D, Cordoba R, Cosyns B, et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229–361.

Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines:  the Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(36):2768–801.

Lancellotti P, Suter TM, López-Fernández T, Galderisi M, Lyon AR, Van der Meer P, Cohen Solal A, Zamorano JL, Jerusalem G, Moonen M, et al. Cardio-oncology services: rationale, organization, and implementation. Eur Heart J. 2019;40(22):1756–63.

del Pozo Cruz B, Ahmadi MN, Lee I-M, Stamatakis E. Prospective associations of Daily Step counts and Intensity with Cancer and Cardiovascular Disease incidence and mortality and all-cause mortality. JAMA Intern Med. 2022;182(11):1139–48.

Townsend N, Kazakiewicz D, Lucy Wright F, Timmis A, Huculeci R, Torbica A, Gale CP, Achenbach S, Weidinger F, Vardas P. Epidemiology of cardiovascular disease in Europe. Nat Reviews Cardiol. 2022;19(2):133–43.

Wang Y, Liu B, Han H, Hu Y, Zhu L, Rimm EB, Hu FB, Sun Q. Associations between plant-based dietary patterns and risks of type 2 diabetes, cardiovascular disease, cancer, and mortality– a systematic review and meta-analysis. Nutr J. 2023;22(1):46.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Curtin LR, Mohadjer LK, Dohrmann SM, Montaquila JM, Kruszan-Moran D, Mirel LB, Carroll MD, Hirsch R, Schober S, Johnson CL. The National Health and Nutrition Examination Survey: Sample Design, 1999–2006. Vital and health statistics Series 2, Data evaluation and methods research 2012(155):1–39.

Curtin LR, Mohadjer LK, Dohrmann SM, Kruszon-Moran D, Mirel LB, Carroll MD, Hirsch R, Burt VL, Johnson CL. National Health and Nutrition Examination Survey: sample design, 2007–2010. Vital Health Stat Ser 2 Data Evaluation Methods Res 2013(160):1–23.

Johnson CL, Dohrmann SM, Burt VL, Mohadjer LK. National health and nutrition examination survey: sample design, 2011–2014. Vital Health Stat Ser 2 Data Evaluation Methods Res 2014(162):1–33.

Chen TC, Clark J, Riddles MK, Mohadjer LK, Fakhouri THI. National Health and Nutrition Examination Survey, 2015–2018: Sample Design and Estimation procedures. Vital Health Stat Ser 2 Data Evaluation Methods Res 2020(184):1–35.

Patel CJ, Pho N, McDuffie M, Easton-Marks J, Kothari C, Kohane IS, Avillach P. A database of human exposomes and phenomes from the US National Health and Nutrition Examination Survey. Sci data. 2016;3:160096.

Centers for Disease Control and Prevention (CDC). About the National Health and Nutrition Examination Survey. 2017 https://www.cdcgov/nchs/nhanes/about_nhaneshtm .

Johnson CL, Paulose-Ram R, Ogden CL, Carroll MD, Kruszon-Moran D, Dohrmann SM, Curtin LR. National health and nutrition examination survey: analytic guidelines, 1999–2010. Vital Health Stat Ser 2 Data Evaluation Methods Res 2013(161):1–24.

Pan S, Chen S. Empirical Comparison of Imputation Methods for Multivariate Missing Data in Public Health. Int J Environ Res Public Health 2023, 20(2).

Riley JP, Beattie JM. Palliative care in heart failure: facts and numbers. ESC Heart Fail. 2017;4(2):81–7.

Springer J, Springer JI, Anker SD. Muscle wasting and sarcopenia in heart failure and beyond: update 2017. ESC Heart Fail. 2017;4(4):492–8.

Saitoh M, Dos Santos MR, Emami A, Ishida J, Ebner N, Valentova M, Bekfani T, Sandek A, Lainscak M, Doehner W, et al. Anorexia, functional capacity, and clinical outcome in patients with chronic heart failure: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). ESC Heart Fail. 2017;4(4):448–57.

von Haehling S. Co-morbidities in heart failure beginning to sprout-and no end in sight? Eur J Heart Fail. 2017;19(12):1566–8.

Wong G, Hayen A, Chapman JR, Webster AC, Wang JJ, Mitchell P, Craig JC. Association of CKD and cancer risk in older people. J Am Soc Nephrology: JASN. 2009;20(6):1341–50.

Article   CAS   PubMed Central   Google Scholar  

Hasin T, Gerber Y, McNallan SM, Weston SA, Kushwaha SS, Nelson TJ, Cerhan JR, Roger VL. Patients with heart failure have an increased risk of incident cancer. J Am Coll Cardiol. 2013;62(10):881–6.

Hasin T, Gerber Y, Weston SA, Jiang R, Killian JM, Manemann SM, Cerhan JR, Roger VL. Heart failure after myocardial infarction is Associated with increased risk of Cancer. J Am Coll Cardiol. 2016;68(3):265–71.

Banke A, Schou M, Videbaek L, Møller JE, Torp-Pedersen C, Gustafsson F, Dahl JS, Køber L, Hildebrandt PR, Gislason GH. Incidence of cancer in patients with chronic heart failure: a long-term follow-up study. Eur J Heart Fail. 2016;18(3):260–6.

Malhotra J, Boffetta P. Association of increased Cancer risk with heart failure. J Am Coll Cardiol. 2016;68(3):272–3.

Meijers WC, Maglione M, Bakker SJL, Oberhuber R, Kieneker LM, Jong Sd, Haubner BJ, Nagengast WB, Lyon AR, Vegt Bvd. Heart failure stimulates Tumor Growth by circulating factors. Circulation. 2018;138(7):678–91.

Article   CAS   PubMed   Google Scholar  

Cuomo A, Pirozzi F, Attanasio U, Franco R, Elia F, De Rosa E, Russo M, Ghigo A, Ameri P, Tocchetti CG, et al. Cancer Risk in the Heart failure Population: Epidemiology, mechanisms, and clinical implications. Curr Oncol Rep. 2020;23(1):7.

Soman A, Asha Nair S. Unfolding the cascade of SERPINA3: inflammation to cancer. Biochim et Biophys Acta (BBA) - Reviews Cancer. 2022;1877(5):188760.

Article   CAS   Google Scholar  

Ausoni S, Azzarello G. Development of Cancer in Patients With Heart Failure: How Systemic Inflammation Can Lay the Groundwork. Frontiers in cardiovascular medicine 2020, 7.

Israr MZ, Bernieh D, Salzano A, Cassambai S, Yazaki Y, Heaney LM, Jones DJL, Ng LL, Suzuki T. Association of gut-related metabolites with outcome in acute heart failure. Am Heart J. 2021;234:71–80.

Sloan EK, Priceman SJ, Cox BF, Yu S, Pimentel MA, Tangkanangnukul V, Arevalo JM, Morizono K, Karanikolas BD, Wu L, et al. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 2010;70(18):7042–52.

van Bilsen M, Patel HC, Bauersachs J, Böhm M, Borggrefe M, Brutsaert D, Coats AJS, de Boer RA, de Keulenaer GW, Filippatos GS, et al. The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2017;19(11):1361–78.

Cho IJ, Shin JH, Jung MH, Kang CY, Hwang J, Kwon CH, Kim W, Kim DH, Lee CJ, Kang SH et al. Antihypertensive drugs and the risk of Cancer: a Nationwide Cohort Study. J Clin Med 2021, 10(4).

Barbalata CI, Tefas LR, Achim M, Tomuta I, Porfire AS. Statins in risk-reduction and treatment of cancer. World J Clin Oncol. 2020;11(8):573–88.

Ricco N, Kron SJ. Statins in Cancer Prevention and Therapy. Cancers 2023, 15(15).

Jiang W, Hu J-W, He X-R, Jin W-L, He X-Y. Statins: a repurposed drug to fight cancer. J Experimental Clin Cancer Res. 2021;40(1):241.

Zhou Q, Jiao Z, Liu Y, Devreotes PN, Zhang Z. The effects of statins in patients with advanced-stage cancers - a systematic review and meta-analysis. Front Oncol 2023, 13.

Matusewicz L, Czogalla A, Sikorski AF. Attempts to use statins in cancer therapy: an update. Tumor Biology. 2020;42(7):1010428320941760.

Download references

Acknowledgements

We would like to acknowledge the participants and investigators of National Health and Nutrition Examination Survey. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

There was no funding to state.

Author information

Authors and affiliations.

Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China

Chenliang Ge, Zhiyuan Jiang, Binghua Long, Qingjian Lu & Yan He

You can also search for this author in PubMed   Google Scholar

Contributions

C G chose the topic. Z J, B L, Q L provided methodological support. C G completed the subsequent data analysis and article writing. Y H provided guidance and assistance throughout the process. All authors revised the manuscript for important intellectual content, participated in the decision to submit the manuscript for publication, and approved the final submitted version.

Corresponding author

Correspondence to Yan He .

Ethics declarations

Ethics approval and consent to participate.

The research has followed the Tenets of the Declaration of Helsinki. Ethical considerations have been rigorously followed, with all data sourced from the publicly available NHANES, which obtained informed consent from all participants and received ethical approval from the NCHS Research Ethics Review Board.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Ge, C., Jiang, Z., Long, B. et al. Associations between cardiovascular diseases and cancer mortality: insights from a retrospective cohort analysis of NHANES data. BMC Public Health 24 , 1049 (2024). https://doi.org/10.1186/s12889-024-18498-7

Download citation

Received : 22 January 2024

Accepted : 02 April 2024

Published : 15 April 2024

DOI : https://doi.org/10.1186/s12889-024-18498-7

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Cancer mortality
• National health and nutrition examination survey

BMC Public Health

ISSN: 1471-2458

• Submission enquiries: [email protected]
• General enquiries: [email protected]

Maintenance work is planned for Wednesday 1st May 2024 from 9:00am to 11:00am (BST).

During this time, the performance of our website may be affected - searches may run slowly and some pages may be temporarily unavailable. If this happens, please try refreshing your web browser or try waiting two to three minutes before trying again.

We apologise for any inconvenience this might cause and thank you for your patience.

Chemical Science

A tumor-targetable nir probe with photoaffinity crosslinking characteristics for enhanced imaging-guided cancer phototherapy †.

* Corresponding authors

a State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, P. R. China E-mail: [email protected] , [email protected]

Spatiotemporally manipulating the in situ immobilization of theranostic agents within cancer cells to improve their bioavailability is highly significant yet challenging in tumor diagnosis and treatment. Herein, as a proof-of concept, we for the first time report a tumor-targetable near-infrared (NIR) probe DACF with photoaffinity crosslinking characteristics for enhanced tumor imaging and therapeutic applications. This probe possesses great tumor-targeting capability, intensive NIR/photoacoustic (PA) signals, and a predominant photothermal effect, allowing for sensitive imaging and effective photothermal therapy (PTT) of tumors. Most notably, upon 405 nm laser illumination, DACF could be covalently immobilized within tumor cells through a photocrosslinking reaction between photolabile diazirine groups and surrounding biomolecules resulting in enhanced tumor accumulation and prolonged retention simultaneously, which significantly facilitates the imaging and PTT efficacy of tumor in vivo . We therefore believe that our current approach would provide a new insight for achieving precise cancer theranostics.

Supplementary files

• Supplementary information PDF (3072K)

Article information

Download Citation

Permissions.

A tumor-targetable NIR probe with photoaffinity crosslinking characteristics for enhanced imaging-guided cancer phototherapy

R. Sun, Y. Zhang, Y. Gao, M. Zhao, A. Wang, J. Zhu, X. Cheng and H. Shi, Chem. Sci. , 2023,  14 , 2369 DOI: 10.1039/D2SC06413H

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence . You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication , please go to the Copyright Clearance Center request page .

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page .

Read more about how to correctly acknowledge RSC content .

Social activity

Search articles by author, advertisements.

New study uncovers lasting financial hardship associated with cancer diagnosis for working-age adults in the U.S.

A new study led by researchers at the American Cancer Society (ACS) highlights the lasting financial impact of a cancer diagnosis for many working-age adults and their families in the United States. It shows a cancer diagnosis and the time required for its treatment can result in employment disruptions, loss of household income and loss of employment-based health insurance coverage, leading to financial hardship. When combined with high out-of-pocket costs for cancer care, nearly 60% of working-age cancer survivors report at least one type of financial hardship, such as being unable to afford medical bills, distress and worry, or delaying or forgoing needed care because of cost. The findings are published in CA: A Cancer Journal for Clinicians.

"While the rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well-documented in the United States, little attention has been paid to how employment and household income can be affected by a cancer diagnosis and treatment," said lead study author Dr. Robin Yabroff, scientific vice president, health services research at the American Cancer Society. "With nearly half of cancer survivors of working age and not yet age-eligible for Medicare coverage, understanding the potential effects of cancer diagnosis and treatment on employment, income, and access to employer-based health insurance coverage is essential."

Study researchers used a composite patient case to illustrate the potential adverse consequences of cancer diagnosis and treatment, including employment disruptions while receiving cancer care, loss of income for unpaid time away from work, and loss of access to employment-based health insurance coverage, if unable to maintain employment. The authors also summarize existing research and provide nationally representative estimates of multiple aspects of financial hardship from 2019-2021, the most recently available years of the National Health Interview Survey (NHIS). The NHIS collects information about health conditions, including but not limited to cancer diagnoses, health status, employment, health insurance, socioeconomic status and experience with health care from nearly 90,000 individuals in 35,000 households each year.

"There are opportunities for a variety of stakeholders to mitigate financial hardship and assist patients with cancer and their families," added Dr. Yabroff. "Federal, state and local policies can increase availability of comprehensive and affordable health insurance coverage and ensure job protections for working adults."

"Today's findings reiterate the critical role access to affordable, quality care and paid family medical leave plays in reducing the financial toll of cancer on those diagnosed -- particularly while they are of working age," said Lisa Lacasse, president of the American Cancer Society Cancer Action Network (ACS CAN). "A majority of cancer patients and survivors (74%) report being forced to miss work due to their illness, most of whom report missing more than four weeks of work, according to an ACS CAN study. No one should be forced to choose between their treatment and their employment. To truly protect patients from the high costs of cancer, Congress must enact paid family and medical leave as well as provide tangible options for affordable health coverage outside of employer-sponsored plans by making permanent the enhanced Marketplace subsidies that allow millions who otherwise have no affordable coverage option to enroll in Marketplace plans."

Study authors emphasize that employers, cancer care delivery organizations and non-profit organizations can also guide efforts to help patients with cancer avoid financial hardship. Employers can offer robust coverage and benefits options, paid and unpaid leave and other workplace accommodations to help reduce employment disruptions and loss of income during cancer treatment. Within cancer care delivery, providers can screen patients for financial hardship, connect patients with relevant services, and make referrals for occupational medicine, rehabilitation care and physical therapy to facilitate return to work and usual activities during and after cancer treatment.

Other ACS authors involved in this study include: Jingxuan Zhao, Dr. Xuesong Han and Dr. Zhiyuan Zheng.

• Diseases and Conditions
• Breast Cancer
• Colon Cancer
• Ovarian Cancer
• Public Health
• Industrial Relations
• Education and Employment
• Privacy Issues
• Colorectal cancer
• Physical therapy
• Economic growth
• Breast cancer
• Industrial relations
• Ovarian cancer

Story Source:

Materials provided by American Cancer Society . Note: Content may be edited for style and length.

Journal Reference :

• K. Robin Yabroff, Joanna F. Doran, Jingxuan Zhao, Fumiko Chino, Ya‐Chen Tina Shih, Xuesong Han, Zhiyuan Zheng, Cathy J. Bradley, Monica F. Bryant. Cancer diagnosis and treatment in working‐age adults: Implications for employment, health insurance coverage, and financial hardship in the United States . CA: A Cancer Journal for Clinicians , 2024; DOI: 10.3322/caac.21837

Cite This Page :

Explore More

• Fossil Frogs Share Their Skincare Secrets
• Fussy Eater? Most Parents Play Short Order Cook
• Precise Time Measurement: Superradiant Atoms
• Artificial Cells That Act Like Living Cells
• Affordable and Targeted Anticancer Agent
• This Alloy Is Kinky
• Giant Galactic Explosion: Galaxy Pollution
• Flare Erupting Around a Black Hole
• Two Species Interbreeding Created New Butterfly
• Warming Antarctic Deep-Sea and Sea Level Rise

Trending Topics

Strange & offbeat.

Cancer patients can now be 'matched' to best treatment with DNA and lab-dish experiments

Identifying the most effective cancer treatment for a given patient from the get-go can help improve outcomes.

Despite many efforts to find better, more effective ways to treat cancer, it remains a  leading cause of death by disease  among children in the U.S.

Cancer patients are also getting younger. Cancer diagnoses among those under 50 has risen by  about 80% worldwide  over the past 30 years. As of 2023, cancer is the  second-leading cause of death  both in the U.S. and around the world. While death rates from cancer have decreased over the past few decades,  about 1 in 3 patients in the U.S.  and  1 in 2 patients worldwide  still die from cancer.

Despite advances in standard cancer treatments, many cancer patients still face uncertain outcomes when these treatments prove ineffective. Depending on the stage and location of the cancer and the patient's medical history, most cancer types are treated with a mix of radiation, surgery and drugs. But if those standard treatments fail, patients and doctors enter a trial-and-error maze where effective treatments become difficult to predict because of limited information on the patient's cancer.

My mission as a  cancer researcher  is to build a personalized guide of the most effective drugs for every cancer patient. My team and I do this by testing different medications on a patient's own cancer cells before administering treatment, tailoring therapies that are most likely to selectively kill tumors while minimizing toxic effects.

In our newly published results of the first clinical trial combining drug sensitivity testing with DNA testing to identify effective treatments in children with cancer, an approach called  functional precision medicine , we found this approach  can help match patients  with more FDA-approved treatment options and significantly improve outcomes.

What is functional precision medicine?

Even though two people with the same cancer might get the same medicine, they can have very different outcomes. Because each patient's tumor is unique, it can be challenging to know which treatment works best.

To solve this problem, doctors analyze DNA mutations in the patient's tumor, blood or saliva to match cancer medicines to patients. This approach is called  precision medicine . However, the relationship between cancer DNA and how effective medicines will be against them is very complex. Matching medications to patients based on a single mutation overlooks other genetic and nongenetic mechanisms that influence how cells respond to drugs.

Sign up for the Live Science daily newsletter now

Get the world’s most fascinating discoveries delivered straight to your inbox.

How to best match medicines to patients through DNA is still a major challenge. Overall,  only 10% of cancer patients   experience a clinical benefit  from treatments matched to tumor DNA mutations.

Functional precision medicine takes a different approach to personalizing treatments. My team and I take a sample of a patient's cancer cells from a biopsy, grow the cells in the lab and expose them to over 100 drugs approved by the Food and Drug Administration. In this process, called  drug sensitivity testing , we look for the medications that kill the cancer cells.

New clinical trial results

Providing functional precision medicine to cancer patients  in real life  is very challenging. Off-label use of drugs and financial restrictions are key barriers. The health of cancer patients can also deteriorate rapidly, and physicians may be hesitant to try new methods.

But this is starting to change. Two teams in Europe recently showed that functional precision medicine could match effective treatments to  about 55% of   adult patients  with blood cancers such as leukemia and lymphoma that did not respond to standard treatments.

Most recently, my team's clinical trial  focused on childhood cancer patients  whose cancer came back or didn't respond to treatment. We applied our functional precision medicine approach to 25 patients with different types of cancer.

Our trial showed that we could provide treatment options for almost all patients in less than two weeks. My colleague  Arlet Maria Acanda de la Rocha  was instrumental in helping return drug sensitivity data to patients as fast as possible. We were able to provide test results within 10 days of receiving a sample, compared with the roughly 30 days that standard genomic testing results that focus on identifying specific cancer mutations typically take to process.

Most importantly, our study showed that  83% of cancer patients  who received treatments guided by our approach had clinical benefit, including improved response and survival.

Expanding into the real world

Functional precision medicine opens new paths to understanding how cancer drugs can be better matched to patients. Although doctors can read any patient's DNA today, interpreting the results to understand how a patient will respond to cancer treatment is much more challenging. Combining drug sensitivity testing with DNA analysis can help personalize cancer treatments for each patient.

I, along with colleague  Noah E. Berlow , have started to add artificial intelligence to our functional precision medicine program. AI enables us to analyze each patient's data to better match them with tailored treatments and drug combinations. AI also allows us to understand the complex relationships between DNA mutations within tumors and how different treatments will affect them.

— 'Very concerning': Microplastics can accumulate in cancer cells and may help them spread, study hints

— Gut bacteria linked to colorectal cancer in young people

— New mRNA 'cancer vaccine' trial launches in UK

My team and I have  started two   clinical trials  to expand the results of our previous studies on providing treatment recommendations through functional precision medicine. We're recruiting a larger cohort of adults and children with cancers that have come back or are resistant to treatment.

The more data we have, the easier it will become to understand how to best treat cancer and ultimately help more patients access personalized cancer treatments.

This edited article is republished from The Conversation under a Creative Commons license. Read the original article .

Diana Azzam is an Assistant Professor and Research Director of the newly established Center for Advancing Personalized Cancer Treatments (CAPCT) at Florida International University. She has a Masters in Biochemistry from the American University of Beirut, Lebanon and a PhD in Biochemistry & Molecular Biology from the University of Miami, Florida. Her lab focuses on implementing functional precision medicine (FPM) approaches in adult and pediatric cancer patients that have run out of treatment options. Working with local hospitals including Nicklaus Children's Hospital and Cleveland Clinic Florida, her lab delivers individualized treatment plans based on a patient's cancer genomic profile and ex vivo drug response. She is currently engaged in two clinical studies to assess feasibility and clinical utility of FPM in relapsed/refractory patients with childhood cancer (ClinicalTrials.gov registration: NCT05857969) and adult cancer (ClinicalTrials.gov registration: NCT06024603). She is working on setting up the first CLIA-certified lab in the State of Florida dedicated for functional cancer drug testing. Her goal is to launch large-scale prospective multi-center randomized clinical trials to better assess efficacy of FPM approaches in the treatment of refractory/relapsed cancers. In parallel, she is working on utilizing FPM as a tool to reduce health disparities in childhood cancer patients from minority populations. She is also integrating a novel machine learning approach to identify specific biomarkers among minority populations that can be targeted using FDA-approved drugs. Her lab also investigates cancer stem cells and how they may result from chronic environmental exposures to toxic metals such as arsenic.

Detecting cancer in minutes possible with just a drop of dried blood and new test, study hints

Catherine, Princess of Wales, announces cancer diagnosis

Claude 3 Opus has stunned AI researchers with its intellect and 'self-awareness' — does this mean it can think for itself?

Most Popular

• 2 Haunting photo of Earth and moon snapped by China's experimental lunar satellites
• 3 Dying SpaceX rocket tears blood-red 'hole' in the sky over Texas — again
• 4 Global 'time signals' subtly shifted as the total solar eclipse reshaped Earth's upper atmosphere, new data shows
• 5 Rare 'porcelain gallbladder' found in 100-year-old unmarked grave at Mississippi mental asylum cemetery
• 2 Scientists create 'toxic AI' that is rewarded for thinking up the worst possible questions we could imagine
• 3 4 solar flares simultaneously erupt from the sun in rare 'super' explosion — and Earth could be hit by the fallout
• 4 NASA reveals 'glass-smooth lake of cooling lava' on surface of Jupiter's moon Io
• 5 'We were in disbelief': Antarctica is behaving in a way we've never seen before. Can it recover?

• See us on facebook
• See us on twitter
• See us on youtube
• See us on linkedin
• See us on instagram

Chuck Chan, stem cell researcher who discovered how to regrow cartilage, dies at 48

The Stanford Medicine researcher was known for his groundbreaking work and his generous spirit as a mentor and colleague.

April 23, 2024 - By Jennifer Welsh

Chuck Chan on a road trip to Yellowstone National Park. Wan-Jun Lu

Charles “Chuck” Kwok Fai Chan, PhD, an assistant professor of surgery at Stanford Medicine, died March 12 at Stanford Hospital surrounded by his wife, parents, siblings, and some of his dearest friends and colleagues. He was 48. 

“Chuck accomplished a great deal in the short time he had,” said   Lloyd Minor , MD, dean of the Stanford School of Medicine and vice president for medical affairs at Stanford University. “He knew he was working against the clock, which drove him to persevere in his research. He leaves behind a wealth of foundational stem cell discoveries that will inform the future of rejuvenative medicine. Stanford Medicine mourns the loss of such a talented researcher at such an early age.”

A member of the Stanford  Institute for Stem Cell Biology and Regenerative Medicine , Chan discovered the mouse and human stem cells that give rise to bone, cartilage and some types of cells that nurture blood-forming stem and progenitor cells. These stem cells are integral to developing new healing technologies for joints affected by osteoarthritis or skeletal injuries. 

​“Chan was an outstanding scientist with a prodigious intellect and curiosity. He was a giant in the field who we lost way too early,” said  Michael Longaker , MD, a professor of plastic and reconstructive surgery and the Deane P. and Louise Mitchell Professor in the School of Medicine. “His work will have a long-lived impact. Decades from now, millions of people with arthritis may be benefiting from his discoveries, and I will say, ‘This work traces back to the Chan lab.’”

Chan trained many young scientists, including undergraduates,  CIRM scholars  and international students. His colleagues said he was generous with his time, ideas and the secret recipes used in his experiments. He believed there were always more discoveries to make and more  Nature  papers to write. 

“He was very confident that there was enough science to go around. He was so willing to share, to talk about science, to collaborate because he was confident that there was so much still to discover,” said his brother  Ed Chan , a researcher in the plastic and reconstructive surgery department at Stanford Medicine. “He was very open with his science, pushing his teams to present their research and share what they discovered and the new tools they developed.”

Chan identified and isolated essential components needed to encourage the development of skeletal stem cells, which can make bone, cartilage and helper cells for blood-cell precursors. To bring these findings to the clinic, he dabbled in gene editing and even a project using microneedle-based technologies for repairing cartilage with his brother.

“He was a brilliant young scientist, unafraid to explore new technology,” said  Irving Weissman , MD, founding director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine, professor of pathology and developmental biology, and the Virginia and D.K. Ludwig Professor in Clinical Investigation in Cancer Research. “Though he didn’t treat patients, he was always thinking about how they’d benefit from his discoveries. We will miss his drive, his empathy, his deep intelligence. Sadly, generations of patients will miss his potential discoveries.”

Boundless curiosity, unrestrained imagination

When he applied to Stanford Medicine’s graduate program, Chan wrote in his personal statement, “If I cannot be a child, then let me be a scientist…scientists have boundless curiosity and an unrestrained imagination.” It was a definition Chan embodied his entire life, friends and family say. 

Though he didn’t treat patients, he was always thinking about how they’d benefit from his discoveries.

Born May 14, 1975, in Hong Kong, Chan moved to the U.S. in early 1982, landing in Anaheim, California, where he could see Disneyland’s famous fireworks displays from his living room window. He was the eldest of six siblings — he had four brothers and one sister. His mother is a homemaker, and his father was in the photographic equipment business during his youth.

“Chuck was the leader of our gang. He was No. 1,” Ed Chan said. “He was always into science — he had a big rock collection; he was into bugs and how the ecosystem works. As a family, we used to laugh at him a bit for his obsessions.”

He attended Alhambra High School, where he played clarinet in the marching band. He started his research career in high school, interning at university labs over the summer. 

He earned a bachelor’s degree in molecular biology from the University of California, Berkeley, in 1999, staying on for two years to complete a research project and publish his work. In 2002, he enrolled in the development biology program at Stanford Medicine, joiningWeissman’s lab, where he focused on finding and defining interactions between stem cells that lead to regenerative growth. He earned his PhD in 2011. 

“He explored many things and proved himself to be absolutely fearless in terms of technologies that might advance the field,” Weissman said. 

As a graduate student, Chan was diagnosed with non-Hodgkin’s lymphoma and underwent extensive treatments. “During that time, he did not stop doing science,” said his wife,  Wan-Jin Lu,  PhD, a research scientist at the Stanford  Institute for Stem Cell Biology and Regenerative Medicine . “He managed to publish a paper, defend his thesis, attend lab meetings and support his lab mates.”

Eventually, a bone marrow transplant from his sister gave him an eight-year remission. He was awarded with an independent Siebel Scholar position and built up his lab immediately after earning his PhD. His work focused on the stem cells that give rise to bones and cartilage. 

“Anyone else might have been demoralized by how hard these experiments were. But Chuck seemed like he couldn’t get enough of it,” Longaker said. “That’s what made him a unique and uber-successful scientist.”

Chan worked doggedly to identify the  mouse skeletal stem cell , which gives rise to the spongy bone that supports blood, hard bone and cartilage.

“Irv said these experiments would not work, but Chuck did not listen. He went ahead and tried it anyway,” Lu said. Eventually, he grew a piece of bone with a spongey inside and cartilage at the ends. “He was so proud of himself that he brought the bone straight into Irv’s office — it was his once-in-a-lifetime ‘Eureka’ moment that every scientist dreams about.”

Weissman added, “One of the unique aspects of helping great graduate students is that they discover what you doubted.”

That work was published in the top journal  Cell  and immediately put him on the map as a “researcher to follow,” Longaker said. Very quickly after that, he identified the human skeletal stem cell, again publishing the finding in  Cell .

“He became this iconic bone biology person early in his career — it was a testament to his vision for what’s possible,” Longaker said. “He went on to regenerate cartilage and reverse the slow healing of aging.”

When joint cartilage has worn away, bone painfully rubs against bone. Often, a patient’s only solution is pain medication or joint replacement surgery. Chan’s research may lead to ways to regrow cartilage.

“Because he had overcome so much with his health as a grad student, I think it gave him a sense of urgency in his work,” Longaker said. “He wasn’t on faculty long. But wow, his contributions will live forever.”

A lasting impression

Not only was Chan a dedicated scientist; he was an optimist inside and outside the lab — an upbeat person always happy to collaborate, colleagues said. He was also a well-known night owl, sending texts from the lab at all hours.

In the lab, Chuck was in his element. That was what he wanted to do with the people he wanted to do it with.

He took an unusual approach to picking his projects. He pursued the fundamental questions, pushing through ideas at an unusually fast rate. He conducted one experiment, focusing on one question, to decide if that project would work. If not, the next week, he would start a new project.

“He didn’t work on small projects. He wanted to make a difference,” Longaker said. “He was undaunted; no matter how complicated the experiment, he did whatever it took — that’s what made him unique.”

Chan was also a good mentor and group leader. “If someone was having a bad day, they would come to Chuck’s lab. They’d have a few beers, and he would help them through it. He would sit with you and inspire you,” Lu said.

Chan spent about 90% of his time talking about, thinking about or conducting lab work, Lu said.

“The idea of work-life balance wasn’t his focus. It’s work and life, they’re just together,” Ed Chan said. “In the lab, Chuck was in his element. That was what he wanted to do with the people he wanted to do it with.”

Outside the lab, Chuck found a profound connection with Hawaiian culture during a weeklong camping trip along the Maui coastline. This experience ignited a love for the Aloha spirit and the Hawaiian way of life. He was often seen in Hawaiian shirts, spending time at the beach and hiking the island trails. Chuck had a particular fondness for sea turtles, always seizing the chance to seek them out along the sandy shores.

When it came to his family, Chuck was the sterner older brother, Ed said. He pushed his younger siblings hard when they were younger, prepping them to take the SATs by having his siblings live with him for the summer and drilling them every day. “They hated it. But to this day, they all admit that they got into decent schools because Chuck was riding them so hard,”Ed Chan said.

Chan received a Siebel Scholarship Award from 2011 to 2013, a Prostate Cancer Foundation Young Investigator Award from 2013 to 2016, a National Institutes of Health Pathway to Independence Award from 2015 to 2020, and an American Federation for Aging Research and Arthritis National Foundation grant in 2018 and 2020. 

Chan is survived by his wife, Wan-Jin Lu, of Redwood City, California; parents Albert and Anna Chan; and his five siblings: Edward Chan, Andrew Chan, Marvin Chan, Brian Chan and Karen Haas. He has nine nephews and nieces.

• Jennifer Welsh Jennifer Welsh is a freelance writer

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

Artificial intelligence

Exploring ways AI is applied to health care