cancer experience essay

Cancer Unwrapped is an annual teen essay writing contest, where teens share their impactful experience with cancer – whether it’s a personal diagnosis or that of a loved one.

Our 2024 contest is now closed.

Winners will be announced in early may.

To determine our winners each year, essays are read and reviewed by a diverse group of judges. 

About Cancer Unwrapped

Learning about a cancer diagnosis – your own or that of a loved one – can cause a storm of emotions, and everyone experiences it differently. We want to know what this experience was like for you.

Did you feel angry, sad, lonely, or maybe something you didn’t expect? What happened in your life, and did it change you or your perspectives?

We invite you to submit a short essay about your experience with cancer for the opportunity to win cash prizes. Since the contest began in 2006, we have received over 8,100 submissions and handed out over $300,000 in prize money to teens.

Over the years we have received stories of triumph and stories of great loss, stories written in times of turbulence, and stories written in times of quiet reflection. Each one has been honest, heartfelt, and unique.

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Winning Essays

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Listen to a teen read her winning essay on our podcast:

Contest eligibility & guidelines.

• Open to teens in the United States in grades 9-12
• Essay length should not exceed 1,500 words.
• Not eligible: poems, essays about a pet, or fiction
• Essays must be original content of the author and in their own voice
• Cash prizes of $1,000 will be awarded to the winners (winners will be asked to fill out a IRS W-9 form).
• Winners will be invited to a virtual reception and asked to read their essays

Judging Process

Tips for writing.

Check out some online communities, resources, tips, and tools to help you tell your story.

Every year, we read incredible stories written by teens from all over the country about their experiences with cancer. We have compiled them here to share with you. 

Our $1000 cash awards are made possible through the generosity of several major donors: The Lucky Seven Foundation, Sally Nordstrom

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Paige Hansen-Shankar Program Manager, Cancer Unwrapped [email protected]

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Home > Cancer Research Catalyst > Cancer Survivors: In Their Words

Cancer Survivors: In Their Words

This year alone, an estimated 1.8 million people will hear their doctor say they have cancer. The individual impact of each person can be clouded in the vast statistics. In honor of National Cancer Survivor Month,  Cancer Today would like to highlight several personal essays we’ve published from cancer survivors at different stages of their treatment. 

In  this essay , psychiatrist Adam P. Stern’s cerebral processing of his metastatic kidney cancer diagnosis gives rise to piercing questions. When he drops off his 3-year-old son to daycare, he ponders a simple exchange: his son’s request for a routine morning hug before he turns to leave. “Will he remember me, only a little, just enough to mythologize me as a giant who used to carry him up the stairs? As my health declines, will he have to learn to adjust to a dad who used to be like all the other dads but then wasn’t?” he questions. 

In  another essay from a parent with a young child, Amanda Rose Ferraro describes the abrupt change from healthy to not healthy after being diagnosed with acute myeloid leukemia in May 2017. After a 33-day hospital stay, followed by weeklong chemotherapy treatments, Ferraro’s cancer went into remission, but a recurrence required more chemotherapy and a stem cell transplant. Ferraro describes harrowing guilt over being separated from her 3-year-old son, who at one point wanted nothing to do with her. “Giving up control is hard, but not living up to what I thought a mother should be was harder. I had to put myself first, and it was the hardest thing I had ever done,” she writes.

In January 1995, 37-year-old Melvin Mann was diagnosed with chronic myelogenous leukemia, which would eventually mean he would  need to take a chance on a phase I clinical trial that tested an experimental drug called imatinib—a treatment that would go on to receive U.S. Food and Drug Administration approval under the brand name Gleevec. It would also mean trusting a system with a documented history of negligence and abuse of Black people like him: “Many patients, especially some African Americans, are afraid they will be taken advantage of because of past unethical experiments like the infamous Tuskegee syphilis study​,” Mann writes, before describing changes that make current trials safer. Mann’s been on imatinib ever since and has enjoyed watching his daughter become a physician and celebrating 35 years of marriage.

In  another essay , Carly Flumer addresses the absurdity of hearing doctors reassure her that she had a good cancer after she was diagnosed with stage I papillary thyroid cancer in 2017. “What I did hear repeatedly from various physicians was that I had the ‘good cancer,’ and that ‘if you were to have a cancer, thyroid would be the one to get,’” she writes.

In another piece for Cancer Today , Flumer shares  how being diagnosed with cancer just four months after starting a graduate program shaped her education and future career path.

For Liza Bernstein, her breast cancer diagnosis created a paradox as she both acknowledged and denied the disease the opportunity to define who she was. “In the privacy of my own mind, I refused to accept that cancer was part of my identity, even though it was affecting it as surely as erosion transforms the landscape,” she writes . “Out in the world, I’d blurt out, ‘I have cancer,’ because I took questions from acquaintances like ‘How are you, what’s new?’ literally. Answering casual questions with the unvarnished truth wasn’t claiming cancer as my identity. It was an attempt to dismiss the magnitude of it, like saying ‘I have a cold.’” By her third primary breast cancer diagnosis, Bernstein reassesses and moves closer to acceptance as she discovers her role as advocate.

As part of the staff of  Cancer Today , a magazine and online resource for cancer patients, survivors and caregivers, we often refer to a succinct tagline to sum up our mission: “Practical knowledge. Real hope.” Part of providing information is also listening closely to cancer survivors’ experiences. As we celebrate National Cancer Survivor Month, we elevate these voices, and all patients and survivors in their journeys.

Cancer Today is a magazine and online resource for cancer patients, survivors, and caregivers published by the American Association for Cancer Research.  Subscriptions to the magazine are free ​ to cancer patients, survivors and caregivers who live in the U.S. 

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The Cancer Experience

The doctor, the patient, the journey.

Roy B. Sessions M.D. on March 13, 2017

Physician Assisted Suicide is but a subdivision of euthanasia, and as quality of death becomes a more relevant societal issue, legal and political pressure for it will grow.

Roy B. Sessions M.D. on August 26, 2016

Not surprisingly, suicide is an avenue of escape for more cancer patients than an equal cohort of their healthy counterparts. The cancer team must be alert to subtle warnings.

Roy B. Sessions M.D. on July 17, 2016

The decision to terminate or not is the sole property of the mother, but with steady leadership of her oncologist. Personal moral codes juxtaposed to survival instincts are at play

Roy B. Sessions M.D. on June 20, 2016

There are sometimes difficult decisions to be made when a pregnant woman develops cancer and conversely when a woman under cancer treatment becomes pregnant.

Roy B. Sessions M.D. on May 26, 2016

The hippocratic principals of antiquity are to a great extent applicable in today's society. We examine the adaptations that have occurred and are currently being scrutinized

Roy B. Sessions M.D. on August 22, 2014

The cancer experience (including treatment and emotional aftermath) can and often alter the sex life of both the patient and partner. The two are not, however, mutually exclusive, depending on the specific cancer and the relationship of the partners.

Roy B. Sessions M.D. on June 28, 2014

Expediency in the referral of cancer patients to cancer specialists relates to minimizing patient anxiety, rather than a need to start treatment quickly.

Roy B. Sessions M.D. on March 23, 2014

Society and the health care system are changing dramatically; and in an attempt to idealize the interaction between the profession and the society, the basics of the adjustments should focus on the repair of the doctor/patient relationship. The physician's role should be view as a higher calling- a vocation - and their expected moral and ethical behavior should reflect it.

Roy B. Sessions M.D. on January 19, 2014

Having and treating cancer is a stressful and physically demanding experience that alters the balance of one's life—sometimes in a depressing and negative way, while others turn it into positive energy and lifestyle changes. This blog reflects the latter of the post cancer effects.

Roy B. Sessions M.D. on December 8, 2013

On occasions, cancer patients perceive (sometimes correctly) that the treatment is worse than the disease, or even death. After full disclosure, the oncologist should support this quest for autonomy—realizing that what we do should be about the patient, rather than the doctor.

Integrative Medicine

Roy B. Sessions M.D. on November 11, 2013

In the October blog, I published a significant statistic that was inaccurate. This is an important correction

Roy B. Sessions M.D. on October 24, 2013

Public awareness and individual cancer patient should be initiated by the medical profession, and the societal system should provide life long stimulation and emphasis on the importance of public knowledge. This will prove cost effective; prevention and early detection save lives and money in the long run.

Roy B. Sessions M.D. on September 9, 2013

While alluring, alternative cancer treatments are, by and large, not yet scientifically proven. Until properly investigated, such methods should not be used. That said, it is important that we remain open to and interested in promoting innovative and unconventional ideas.

Spirituality

Roy B. Sessions M.D. on July 18, 2013

Facing death and enduring cancer is influenced by many factors, not the least of which is a patient's belief about divinity and the after life. That this is solely psychological is unclear and may involve brain neurochemistry, according to some investigators.

Roy B. Sessions M.D. on June 15, 2013

Doctors and patients share the human characteristic of being affected by their attitudes and surroundings. In each, the cancer experience of a patient is altered, some positively and some negatively. This essay begins to look at what influences the coping skills of patients, and the impact on the frightening experience of having cancer.

Roy B. Sessions M.D. on May 14, 2013

This continuation of the series on communication begins to introduce practical methods to specific types of people, and also begins to consider those dealings that include the patient's family.

Roy B. Sessions M.D. on April 4, 2013

The continuum of our discussion on communication between doctor and patient has thus far dealt with the importance of that state and what actually constitutes the ideal. Today's blog is more an attempt to explain what influences the doctor ability to lead and help develop the relationship so important to the cancer experience.

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Roy B. Sessions M.D. on March 7, 2013

The establishment of and the necessary adjustments in the relationship between oncologist and patient is ideally a priority item. Absent the right human chemistry, the long and trying treatment of a given cancer can be substantially more difficult. Things don't always go as designed and then, the ability to fall back on solid human relationships assumes importance

Roy B. Sessions M.D. on February 10, 2013

Essentials of doctor-patient are especially important in cancer patients, and achieving ideal communication, while not easy, renders the whole cancer experience infinitely more tolerable.

Roy B. Sessions M.D. on January 4, 2013

Without patient comprehension, a doctor cannot claim to have communicated. Anything less than patient is only medical monolog, and it is the doctor's responsibility to achieve this state. In the world of cancer care, fear is an ever lurking companion for patients, and the better the process of explanation and communication, the less the fear. Ignorance is not bliss.

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Cancer.Net Podcasts

3 tips on writing about your cancer experience.

Voices on Cancer  is a Cancer.Net Blog series where advocates share their stories and the lessons they have learned about being a cancer advocate. Andrea Hutton is a breast cancer survivor and patient advocate. Her advocacy efforts focus on empowering and educating women to take care of their health. In her book Bald is Better With Earrings , she talks about her cancer experience and offers advice to women with breast cancer.

My advocacy story

When I heard the heart-stopping words, "It's cancer," I was a 41-year-old with 2 children and a busy life.

Being diagnosed with stage IV breast cancer changed my life and body forever. I was immediately thrown into a medical vortex . If I wasn't at a doctor's office, I was on hold with a doctor's office or online researching a doctor's office. I lost my hair, a breast, and more than a year of my life to tests, surgery, chemotherapy, and radiation therapy. Of course, it didn't end there. That pink elephant with the word "cancer" on it never leaves the room.

When I was diagnosed, I wanted to know everything. I wished I had a girlfriend's guide to breast cancer. While undergoing treatment, I started a blog to keep my friends and family up to date. I used the blog to try to explain what I was going through and share the tricks and tips I was discovering along the way.

Don’t shy away from support

I've been touched by how many people have reached out to me since my book was published.  Recently, I heard from Tiffany, a woman whose doctor found a spot on an MRI a year after she finished her cancer treatment. Tiffany and her husband were getting ready to go on a trip when she received the news. She wasn't sure if she should tell him. She was devastated, but she didn’t want him to worry. She thought she was supposed to be brave and forgo the support she desperately needed — the support that studies show actually helps women do better while in treatment.

We are bombarded with the idea of the “perfect” breast cancer patient. In other words, a warrior who only eats organic food, wears just the right amount of makeup, proudly goes bald, founds a local charity, and of course, can walk or run for miles in fundraisers. She doesn't seem to need any help to keep her busy life in order. That’s why it often feels like a breast cancer diagnosis comes with the pressure to be perfect while fighting for your life. It’s easy to get brainwashed into thinking we have to constantly act like warriors.  

Through my own cancer experience, I learned some hard lessons about who I am and what I need. I learned about my resilience and, in turn, my limits. I gave myself permission to have limits. I had to learn how not to push myself and how to ask for help. It's not just about you. People around you want to feel like they're doing something to help, so try to let them.

Women like Tiffany motivated me to become a patient advocate. I've been so inspired by the women I meet who fight for their lives every day. They and their daughters deserve a future without fear — a future where we no longer need so much awareness . We need to remind people that breast cancer is not a cause. It is a real disease that affects real women and men every single day—not just in October, when it’s National Breast Cancer Awareness month.

Writing about your cancer experience

In the beginning, I wrote a blog just to keep my friends and family from calling 8 times a day. But I also found writing about my experiences to be helpful for my own sanity. It gave me an outlet to share my emotions and information about my treatment. It even led me to a new career.

Here are a few tips on penning your thoughts after diagnosis.

Start a blog. Try setting up a blog to tell everyone how and what you’re doing. Make it your goal to write something every day. It doesn’t have to be a lot. It can even be a few lines or a photo. It’s easy to create your blog on websites such as CaringBridge and MyLifeLine , where you can make your writing public or private. Keeping a blog can connect you with friends and family. If you make a public one, you never know who may learn from you.

Write for yourself. If a blog isn’t your thing, try keeping a log or journal for yourself about your cancer experience. Include how you’re feeling every day and any questions you have about your health and treatment. Make notes about your energy level. These notes can be invaluable for tracking trends during chemotherapy. Or, they may just be a way for you to keep track, period. Chemobrain is real, I think. I can’t remember!

Seek out support. In addition to using writing as an outlet, find a group that you can talk to about what you're going through. Nobody understands it like someone who has been there. You can connect with a support group in person, online, or by phone. Remember not to take medical advice from anyone without credentials. Not even me!

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Essay on Cancer for Students and Children

500+ words essay on cancer.

Cancer might just be one of the most feared and dreaded diseases. Globally, cancer is responsible for the death of nearly 9.5 million people in 2018. It is the second leading cause of death as per the world health organization. As per studies, in India, we see 1300 deaths due to cancer every day. These statistics are truly astonishing and scary. In the recent few decades, the number of cancer has been increasingly on the rise. So let us take a look at the meaning, causes, and types of cancer in this essay on cancer.

Cancer comes in many forms and types. Cancer is the collective name given to the disease where certain cells of the person’s body start dividing continuously, refusing to stop. These extra cells form when none are needed and they spread into the surrounding tissues and can even form malignant tumors. Cells may break away from such tumors and go and form tumors in other places of the patient’s body.

Types of Cancers

As we know, cancer can actually affect any part or organ of the human body. We all have come across various types of cancer – lung, blood, pancreas, stomach, skin, and so many others. Biologically, however, cancer can be divided into five types specifically – carcinoma, sarcoma, melanoma, lymphoma, leukemia.

Among these, carcinomas are the most diagnosed type. These cancers originate in organs or glands such as lungs, stomach, pancreas, breast, etc. Leukemia is the cancer of the blood, and this does not form any tumors. Sarcomas start in the muscles, bones, tissues or other connective tissues of the body. Lymphomas are the cancer of the white blood cells, i.e. the lymphocytes. And finally, melanoma is when cancer arises in the pigment of the skin.

Get the huge list of more than 500 Essay Topics and Ideas

Causes of Cancer

In most cases, we can never attribute the cause of any cancer to one single factor. The main thing that causes cancer is a substance we know as carcinogens. But how these develop or enters a person’s body will depend on many factors. We can divide the main factors into the following types – biological factors, physical factors, and lifestyle-related factors.

Biological factors involve internal factors such as age, gender, genes, hereditary factors, blood type, skin type, etc. Physical factors refer to environmental exposure of any king to say X-rays, gamma rays, etc. Ad finally lifestyle-related factors refer to substances that introduced carcinogens into our body. These include tobacco, UV radiation, alcohol. smoke, etc. Next, in this essay on cancer lets learn about how we can treat cancer.

Treatment of Cancer

Early diagnosis and immediate medical care in cancer are of utmost importance. When diagnosed in the early stages, then the treatment becomes easier and has more chances of success. The three most common treatment plans are either surgery, radiation therapy or chemotherapy.

If there is a benign tumor, then surgery is performed to remove the mass from the body, hence removing cancer from the body. In radiation therapy, we use radiation (rays) to specially target and kill the cancer cells. Chemotherapy is similar, where we inject the patient with drugs that target and kill the cancer cells. All treatment plans, however, have various side-effects. And aftercare is one of the most important aspects of cancer treatment.

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Cancer Survivor Stories

“Continue looking forward to the future, because none of us know what that will bring,” says Wenora, who has survived several cancers.

“Give yourself leniency. You have to give yourself that room to grow into the new you,” says Mark, who survived Hodgkin lymphoma.

“I wish for everyone to have those people that they can call on,” says Xenia, who survived endometrial and uterine cancers.

“You may not have symptoms,” says Jackie, a lung cancer survivor who never smoked. “So test your house for radon.”

“I had one question, but I was too afraid to ask it: ‘Am I gonna die?’” recalls cervical cancer survivor Ana in this animated video.

“We’ve been given one body, and we must take care of it,” says ovarian cancer survivor Linda in this animated video.

“Ask your loved one how they want to be supported and reassure them that you’re with them all the way,” says Kimberly, whose mother had breast cancer.

Stories by Type of Cancer

Sisters Emily and Caroline have a BRCA gene mutation. They took different paths.

More Breast Cancer Stories

“We need to adopt a mindset that ensures that we are making ourselves a priority,” says Patti.

More Cervical Cancer Stories

“The surgery was successful. But I never would have found it early if I hadn’t been screened,” says Robert.

More Colorectal Cancer Stories

“If my doctor hadn’t acted quickly, the outcome would have been much different,” says Janet.

More Ovarian Cancer Stories

“Listen to your body—it does tell you things. It’s about knowing yourself. Once you know, you can fight it,’” says Lynn.

More Uterine Cancer Stories

“Do not let fear, embarrassment, or shame prevent you from finding the help you need,” says Sarah.

More Vaginal and Vulvar Cancer Stories

Improving Cancer Survivors’ Mental Health Care

Four cancer survivors share their stories about talking to their doctors about mental health issues during and after their cancer treatment.

• Amelia, survivor of acute lymphoblastic leukemia: Watch her video or read her story
• James, survivor of colon cancer: Watch his video or read his story
• Mari, survivor of breast cancer: Watch her video or read her story
• Brock, survivor of multiple myeloma: Watch his video or read his story

Let’s Talk About Breast Cancer Risk

Ten women share their stories about how hereditary breast and ovarian cancer has affected them. Learn about the conversations these women have had, or plan to have, with their family members about their family history of cancer.

How did Jackie, who never smoked, develop lung cancer? She is grateful that she found an answer.

“Only you know your body,” said breast cancer survivor Celeste. “Listen to your inner voice, whatever you may call it.”

“I was a bit surprised, but not shocked,” Lorenzo said when a routine checkup showed his PSA level was high.

“Look for the light at the end of the tunnel, because it is there whether you notice it at first or not,” says Tyler.

“The only person I have hugged since the pandemic has been [my wife] Denise,” says David, a colon cancer survivor.

“It is always okay to ask questions. Navigating this process can be hard,” says Andrea, a breast cancer survivor.

“I fell in love with the sun-assisted caramel color that my Afro Puerto Rican roots blessed me with every summer,” says melanoma survivor Robin.

“Keeping my mind focused and my attitude positive made all the difference in the world,” says breast cancer survivor Ronda.

“The impact of cancer doesn’t stop as soon as treatment is finished,” says Jordyn.

“When you hear the word ‘cancer,’ your world changes in an instant,” says Lewis.

“The doctor asked, ‘How long have you had hepatitis C?’ And I said, ‘I didn’t even know I had it!’” recalls Gary.

George had already survived cancer twice when his doctor told him he had prostate cancer.

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“Now I know there’s no obstacle that I can’t handle. Survivorship means taking charge, understanding what you have to do to take care of yourself, and working with your doctors as a team,” says Jackie, who survived lung cancer.

Podcast [MP3-4.3MB] | Transcript [TXT-3KB]

“I have what I call a ‘new normal.’ That means a different attitude towards life. I do as much as I can by eating well, exercising, and keeping my stress levels down,” says Pam, who survived breast cancer.

Podcast [MP3-4.9MB] | Transcript [TXT-4KB]

“It was the moment when the diagnosis, the treatment, the road behind, the road ahead, all converged. Somewhere from within, we find a strength that helps us to overcome. Cancer did not win,” says Carletta, who survived breast cancer.

Podcast [MP3-24.5MB] | Transcript [TXT-10KB]

Be informed and inspired with stories from survivors of many kinds of cancer.

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The right way to talk with someone who has cancer

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Holidays and family celebrations are a joyous occasion for most people. But for someone with  cancer  or other serious illness, they can be a time of overwhelming anxiety and fear. And as family and friends get together, it's important to show that you care without coming across as insensitive.

Watch this "Mayo Clinic Minute" video to hear Lynne Vitagliano, a clinical social worker at Mayo Clinic, offer some helpful advice to make those uncomfortable conversations less awkward:

Many times, people mean well but don't know the right things to say to someone with cancer.

"Every person is different. So it would be hard to say that there's any one right question to ask or right thing to say. What I think is most important is to convey genuine care and concern," says Vitagliano. "Offer an invitation rather than a question. So to say something along the lines of, 'I've been thinking of you. I know a lot is going on in your life. I'm here if you'd like to talk.'"

Vitagliano says it's also important how you respond. And the best response is simply listening.

"Allow them to talk about their experience without feeling the need to kind of jump in with your own advice or suggestions," she says.

And it's important to show that you care without coming across as insensitive.

"We want to say something that we think is supportive. So we say, 'I'm sure it'll all turn out OK.' Well, we don't know that, and that's not necessarily true. And so, by saying that, it almost invalidates what they've shared with us," Vitagliano says. "It's not as supportive as saying, 'Wow, you've been through so much this year. And I'm just blown away by your strength. What can I do to help?'"

A version of this article was originally published on the Mayo Clinic News Network .

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Dr. Linda Hasadsri's experience with genetic testing and colorectal cancer fuels a passion for helping patients find answers in the laboratory.

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Sally Blackwell was diagnosed with rectal cancer at 33 after her second child was born. The lifesaving care she received inspired her to find work at Mayo Clinic.

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Essay on Cancer

List of essays on cancer, essay on cancer – introduction, types and conclusion (essay 1 – 150 words), essay on cancer (essay 2 – 250 words), essay on cancer – for school students (essay 3 – 300 words), essay on cancer – for medical students (essay 4 – 400 words), essay on cancer – for science students (essay 5 – 500 words), essay on cancer (essay 6 – 600 words), essay on cancer – written in english (essay 7 – 750 words), essay on cancer – for ias, civil services, upsc, ips and other competitive exams (essay 8 – 1000 words).

Cancer is a disease which is related to the abnormal growth of cells in a particular part of the body. Since the last decade, cancer has become one of the most feared diseases of all times, particularly due to the difficult treatment one has to undergo and the limitations of the treatment in curing this disease during later stages of cancer.

Audience: The below given essays are exclusively written for school and college students. Furthermore, those students preparing for IAS, IPS, UPSC, Civil Services and other competitive exams can also increase their knowledge by studying these essays.

Introduction:

Cancer is a group of more than 100 diseases that can develop in almost anywhere in the body. Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.

Types of Cancer:

There are various types of cancer. They include:

1] Breast cancer: This is type of cancer that forms in the cells of the breast.

2] Prostate cancer: This is type of cancer that occurs in a man’s prostate. This is a small walnut sized gland that has the duty of producing seminal fluid.

3] Lung cancer: This is a type of cancer that begins in the lungs and this occurs mostly in people who smoke.

4] Leukemia: A cancer of blood forming tissues, hindering the body’s ability to fight infection.

Conclusion:

We have seen various types of cancer but the types of cancer we have are hundreds but we had mentioned just a few. Each type of cancer comes with various symptoms and various ways of curbing it.

Cancer is a disease that has been around for centuries, but it has never had such an impact on public health as it has now. Cancer is the increase in the number of cells in human beings at an abnormal rate. Doctors have been discussing the reasons behind this increase for the past fifty years. One is tempted to think that there are no reasons behind this occurrence and that it is just a natural phenomenon, people die all the time. Right?

The thing is that the number of cancer cases has increased in the past decades and a lot of this increase is attributed to the influence of different types of radiation. Even though most of the really dangerous substances (or sources of radiation) are not allowed near people. What else can be causing such an increase in cancer cases?

Some doctors have made a discovery regarding cancer that can really help us get rid of this problem. Following down the line of the argumentation presented in the famous “China Study” more doctors are advising their patients to change their diet because it can help  in their fight against cancer. Not only that but a proper diet can also be the best prevention.

When you are a student your metabolism is young so you do not feel the bad effect of your habits as much as older people do but as we age the side effects of our bad choices will become obvious. We can teach ourselves to listen to our bodies and to prevent cancer but to do that we, first of all, have to defeat our habits.

Cancer is uncontrolled and unchecked development of abnormal cells in a part of the body. Cancerous cells develop just like another cell in the body. They, however, keep growing and can form a mass then subsequently becomes tumors. Since cells are present in every part of our body, cancer can also grow in all parts of our body.

Causes of Cancer:

One great scientific mystery in our world is the cause of cancer. Scientists from all over have tried and failed in isolating any particular action, substance or environmental factors that can lead to cancer.

However, scientists all over the world agree that cancer is caused by substances known as carcinogens. These substances are introduced to the body when we are exposed to or consume materials containing them. One of the confirmed sources of carcinogens is exposure to radiation from x-ray machines.

Cancer Treatment:

There are various ways to treat a person infected with cancer. These modes of treatment are chosen depending on the type of cancer, the stage of development and the health peculiarities of the cancer patient. In other cases, several modes of treatment are combined to treat a single patient.

Some of the modes of treating cancer are in fly highlighted below:

1. Surgery to remove Cancerous tumors from the body.

2. Radiation therapy to reduce the growth of cells.

3. Chemotherapy for destroying cancer cells.

4. Stem cell transplant.

Prevention of Cancer:

Just as there are no agreed actions, materials and exposure that causes cancer, there are no generally accepted means of preventing cancer. However, there are certain habits that can limit a person’s exposure.

Some of them are highlighted below:

1. Healthy environment and diet.

2. Reduction of exposure from the sun.

3. Keep your weight low.

4. Avoid the use of tobacco.

Early detection of cancer has been hailed as the most potent way of treating this menace. Though scientists are still in the business of searching for a cure, we as humans can prevent cancer by regular medical check-ups.

Cancer is one of the second largest fatal illnesses across the world. One of the horrific words a human being can listen to is being diagnosed with Cancer. The word Cancer brings alarm and anxiety to the listener. Cancer is the abnormal growth of cells in one part of the body which can even spread to other parts if not treated at an early stage. Neoplasms or tumour are the subset of these abnormally grown-up cells which often results in a mass or lump.

What causes Cancer?

Those agents which cause cancer are termed as Carcinogens . These can be classified into physical, chemical and biological. Physical Carcinogens include ultra violet and other ionizing radiations. Food adulterants such as aflatoxin, tobacco smoke, drinking water contaminant such as Arsenic, asbestos etc., are termed as Chemical Carcinogens. Viruses, Bacteria and other parasites which cause infections and eventually lead to Cancer are categorized under Biological Carcinogens. Ageing also causes cancer as the risk of the cellular repair mechanism weakens as we age.

Significant Symptoms of Cancer:

Some of the major symptoms of cancer include unexplained weight loss, extreme fatigue, persistent sores that do not heal, changes in the bladder and bowel movements, odd bleeding and discharges, change in voice due to cancer indication in larynx and lumps and bumps on the skin.

Preventive Measures:

Some of the risk factors which needs to be addressed to prevent cancer may include avoidance of tobacco, being overweight or obese, unhealthy eating with less vegetables and greens, physical in-activity, avoiding pollution etc. Apart from the mentioned, vaccination against HPV and Hepatitis B Virus, controlling hazards while at work, reducing exposure to ultra violet and ionizing radiation etc., can help prevent being infected by Cancer.

Assessing the type of cancer and the stage is very important because every cancer type has a different pattern of treatment from surgery, radiotherapy and chemotherapy . The treatment that is used to relieve the cancer patient from their pain and enhance the quality of life for the patients and their families is termed as Palliative care.

World Health Organization has partnered with UNO and other non-profit organizations to ensure every country is being made aware of the non-communicable diseases and the prevention of cancer and its control. Insights to develop Centers of Excellence to provide quality treatments and to conduct research on the carcinogenesis should be provided to governments and to help the people.

The abnormal cell growth in our body which spreads to other parts as well is what is termed as cancer. Around four lakh of people in India are known to be affected by this disease every year. More so, around half of them are not able to survive as they are usually detected in the last stages of cancer. Hence it is all the more important to educate the people about this disease and its symptoms so that it can be detected early and the lives of the people suffering from it can be saved.

Cancer can affect any body part. The part that is affected gives it the name, for instance, lung cancer which affects the lungs, skin cancer in which the skin is affected and so on. However, we can broadly divide cancer into four types. The first one is Sarcoma which is known to affect the blood vessels, bones, muscles cartilages and connective tissues. The second type of cancer is Carcinoma which affects the internal organs of the body or the skin. The third type is the Lymphoma. This cancer affects the lymph glands and the lymph nodes. The last type in which cancer can be categorised is Leukaemia which largely affects the parts forming blood such as the bone marrow.

Symptoms of Cancer:

Although no particular cause is known to trigger this disease, some activities have been associated as the cause of different types of cancer. The first and foremost is smoking. Excess smoking affects the entire respiratory system thereby leading to the onset of lung cancer. More so chewing tobacco is also attributed to giving rise to mouth and throat cancer. Similarly, alcohol is attributed to be the cause of stomach, liver and gallbladder cancer. Summarising it, all the ill habits of society and urbanisation have been attributed to this disease. Even radiations coming from X-ray machines can prove harmful and lead to cancer. That is why there are proper laws an protection in place when exposing people to these harmful radiations.

Treatments Available:

If detected in early stages, cancer can surely be curable. Surgery is one of the primary steps of curing this disease. If required, doctors remove the body part affected such as the uterus, gallbladder or the breast. Thereafter, through radiotherapy, the cancerous cells on the other affected parts of the body are killed so that they don’t spread to other parts. Chemotherapy is done using the strong chemical in order to kill the cancerous cells. Other methods such as tumour suppressing genes are used in different types of cancer as may be the need advised by the doctors. Whatever the method, it is extremely difficult to go through the pain and social stigma such as loss hair which comes alongside the treatment of cancer.

Living with this Disease:

It is indeed very difficult to live with this disease as not only this disease is not fully curable but the treatment is so tough that it scares even the toughest of individuals. We, as a society, must support the people suffering from cancer and help in their difficult times. We must not discriminate them and must understand that is already suffering a lot and must not do anything which further aggravates their sufferings.

Cancer is a severe disease in which there is abnormal growth of cell that spreads around the human body. Many people in the world are struggling with this disease. Consistently around 10 million cases are analyzed. These number of cases are expected to increase around 20 million by 2020. It turns into the most widely recognized reasons for death. Due to abnormal cell growth, it develops & affects the overall body weight. Prolonged cough and abnormal bleeding are some symptoms of this severe disease. The developed abnormal cells first make their impact on organs then slowly moved as poison. Cancer disease can be identified in the beginning periods. The medical professionals are still trying to catch this disease.

One of the main causes of cancer is smoking. Other causes include tobacco, consumption of alcohol, obesity, lack of physical activities, exposure to UV radiations, etc. Age factor and changes in genes are yet other factors that cause cancer.

Cancer has different types which can be divided into various forms:

i. Skin Cancer:

It is the most common type of cancer which can be seen in many people. Every year more than 1 million people are affected by skin cancer. Skin cancer happens due to the overexposure from the sun. The thicker ozone layers directly harms our skin, which increases the chances of skin cancer.

ii. Lung Cancer:

This type of cancer is related to the cells inside the lungs. The symptoms of this type of cancer are chest pain & sudden weight loss. It is also known as lung carcinoma. As a process of metastasis, the growth of abnormal cell growth spread inside the lungs. Smoking is a fundamental driver of Lung cases.

iii. Kidney Cancer:

Another name of kidney cancer is renal cancer. Renal Cell Carcinoma and Transitional Cell Carcinoma are the types of kidney cancer. This development of cancer happens after the age of 40 years. Smoking can twofold the danger of kidney malignant growth.

iv. Leukemia:

This cancer starts developing in the bone marrow, which leads to a high number of abnormal white cells. Acute myeloid leukemia or acute lymphocytic leukemia are the sorts of leukemia. Chemotherapy or radiation therapy can be used as the treatment for Leukemia.

Cancer Staging:

It is important to understand the staging factor of this severe disease. Diagnosis of cancer in early stages helps to tackle this disease by proper treatments. During the initial stages of cancer, proper surgeries or radiotherapy can help to overcome cancer. When the broken cancer cells move to other parts of the human body, then advance treatment is suggested by the professionals. But when a patient is in the final stages of cancer, he needs a treatment which covers his whole body. Chemotherapy is a therapy which is used to circulate the bloodstream. Professional doctors use various test techniques to identify the stages of cancer. Stages are used to describe the severity of cancer.

In the initial stage, cancer can be prevented through medication, proper surgeries and light treatment. In the advance stages of cancer, chemotherapy and radiation therapy is useful. Above all, the best way to keep cancer away is to stay away from smoking and tobacco, eat healthy food and a lot of green vegetables, and do some physical exercise daily.

It is very difficult for a cancer patient to fight with the final stages of cancer. To deal with this severe problem cancer symptoms should never be ignored. More than 70% of cases are seen only due to smoking. At every stage, it is essential that everyone must adopt a healthy diet plan & exercise daily to prevent this disease. A person who has a good and healthy lifestyle can fight with cancer more strongly.

Current trends in global health mention cancer. Cancer is currently one of the leading causes of death globally. It is an illness in which abnormal cell growth develops and affects parts of the human body as it advances, it has the potential to spread from one part of the body to the other. It is a chronic illness that imposes a great economic burden on a nation because its management is costly. Cancer occurs in different parts of the body and are classified according to where it has affected. In India, men are mostly acted by lung, oral, lip and neck cancers whereas women are affected by cervical, breast and ovarian cancer. The detection procedure varies with the type of cancer while the treatment varies with the stage of the cancer progression. Mostly early stages of cancer have better prognosis compared to late stages of cancer.

There are modifiable and non-modifiable factors that predispose an individual to cancer. Non modifiable factors include age and genetics. With an increase in age, the rate of cancer incidence increases. The genetic predisposition to cancer increases the incidences of suffering the disease. Modifiable factors include lifestyle habits like drinking and smoking tobacco which increase the incidences of lung, oral, esophageal among other cancers. Diet is also a predisposing factor especially one that is less in vitamin supplements.

Physical inactivity and obesity predispose to cancers of the colon, breast and others. Sexual activity in women with multiple sexual partners predisposes them to cervical cancer due to the transmission of HPV (Human Papilloma Virus). The environment also predisposes to cancer because of the chemicals, radicals and radiations that interact with human beings.

Detection of Cancer:

The detection varies with the type of cancer and so screening is done for each type differently. It is advisable that people get regular checkups of the whole body so that early detection facilitates effective and curative treatment. Screening of cancer is done using detailed examination of the physique, laboratory and histology tests, radiological and magnetic imaging techniques among other methods.

The campaigns against cancer advocate for early detection by teaching the public on the early signs of cancer. In breast cancer awareness for example, the public is made aware of physical examination of the breast and if they detect any abnormal growth or lump, they are to seek further investigation. Early detection is important because it results in successful treatment. In the detection, the cancer staging is done, which is usually four stages, stage one, two, three and four. Stage one has the best prognosis whereas stage four has the poorest prognosis.

Treatment of Cancer:

Once cancer is detected, a range of treatment options is provided. Treatment depends on the types of cancer and the staging. It can be treated by surgery whereby excision of the abnormal growth is done. Surgery is done for non-hematological cancers and those that have not metastasized to other parts of the body. An example of surgery is mastectomy to treat breast cancer.

Chemotherapy is another treatment option that involves the administration of anticancer medication that eliminate the abnormal cells in the body. Another treatment option is radiation therapy that uses ionizing radiations to destroy cancer cells. Radiation is also used to make tumors small. It is used to treat solid tumors and it depends on the sensitivity of the tumor to the radiations. It is targeted at the nucleic acid destruction in the tumor cells.

Consequences of Cancer:

Cancer is a chronic illness that could result in very serious consequences even with treatment. Cachexia is the extreme wasting of the body that causes death in cancer patients. Economic burden to both the individual and the nation is experienced in cancer treatment because the treatment modalities are costly. The economic burden results in decline of the nation’s economy and increased healthcare costs to the population.

Mental illnesses result from cancer because it is a terminal illness and most patients become mentally unstable upon diagnosis. The quality of health is affected in a country when there is high incidences of cancer and the performance is greatly affected, which cause poverty and economic crisis for individuals.

Cancer is a serious illness that impacts the lives of people and the nation negatively. It is evident that cancer has diverse treatment options but the problem is that people do not go for checkups. Checkups are important in early detection, which usually results in successful treatment and less burden of cancer in a nation and in individuals.

Cancer is basically an agglomeration of various diseases that involves the abnormal growth of cells with the ability to spread or invade other body parts. Cancers are quite different from benign tumours in that the latter does not spread or invade other body parts. Some of the many symptoms and signs of cancer include abnormal bleeding, a lump, weight loss that is unusual, prolonged cough and bowel movement change. Even though these listed symptoms and signs of cancer, they might be caused by other things so it is necessary to be diagnosed. Today, we have more than 100 various kinds of cancer that affect us humans.

History of Cancer:

It is believed that cancer has been in existence for a majority if not all of the history of man. Breast cancer was the first form of cancer that was recorded and this happened around 1600 BC in Egypt. Between 460 BC and 370 BC, Hippocrates spent time analysing various types of cancer and referred to them as crayfish or crab. The name was as a result of the crab-like look of the malignant tumour and the lateral extension of the distended veins and tumours.

Factors Causing Cancer:

It has been discovered that the major cause of deaths as a result of cancer is the use of tobacco and it accounts for about 22 percent of the total number of deaths due to cancer. Poor diet, obesity, excessive alcohol consumption and a lack of exercise and physical activities accounts for another 10 percent of deaths caused by cancer. Some other causes and factors that contribute to cancer include environmental pollutants, ionizing radiation exposure and certain infections.

In most developing countries, infections like hepatitis B, Helicobacter pylori, papillomavirus infection of humans, Hepatitis C, HIV and Epstein Barr contribute to fifteen percent of all cancers. All of the factors listed above change the cell genes. There are always a lot of genetic changes before the development of cancer. About 10% of all cancers are as a result of genetic defects that are inherited from a parent. Asides the symptoms and signs that are used to detect cancer, screening tests are also a good way of detecting cancer. Cancer is normally thoroughly investigated using medical imaging; it is then confirmed through biopsy.

Development of Cancer:

A tumour or neoplasm is a collection of cells which have gone through growth that is not regulated and most times form a lump or mass. Every tumour cell exhibits the six important characters that are necessary for the production of the malignant tumour.

The six characteristics are:

1. Cell division and growth without all the signals that are proper.

2. Continuous division and growth even though the signals given are contrary.

3. Cell death that is usually programmed is avoided.

4. The divisions of the cell are quite limitless in number.

5. The construction of blood vessel is promoted.

6. The tissues are invaded and metastases are formed.

Cancer Prevention:

The prevention of a lot of cancers can be ensured by trying to maintain a weight that is healthy, not smoking, consuming a lot of whole grains, fruits and vegetable, avoiding the consumption of a lot of alcohol, reduction in the amount of red and processed meat that is consumed, getting vaccinated against some infectious diseases and the avoidance of too much exposure to sunlight. It is sometimes useful that there is early detection in cases of colorectal and cervical cancer and this can be achieved through screening. The usefulness of breast cancer screening is highly controversial.

The treatment of cancer is usually done by combining surgery, radiation therapy, targeted therapy and chemotherapy. A very important element of care is the management of symptoms and pain. In cases of advanced disease, palliative care is of utmost importance. The extent of the disease at the commencement of treatment and also the form of cancer that is involved go a long way to determine the odds of survival. Using the adopted survival rate at five years, children that were under the age of 15 when they were diagnosed have an average rate of survival of 80% in most developed countries. In the US, the average rate of survival for the five year period is 66%.

90.5 million  people were living with different cancers in 2015. It has been reported that every year, close to 15 million reports of new cancer cases are filed. These do not include the cases of skin cancer. Cancer results in more than eight million deaths every year which is about 15.7% of the total number of deaths every year.

In males, prostate cancer, lung cancer, stomach cancer and colorectal cancer are the most widespread cancer types. In females, colorectal cancer, breast cancer, cervical cancer and lung cancer are the most widespread cancer types. Apart from melanoma, if we include skin cancer in the amount of new cases of cancer every year, it is going to be 40% of the total number of cases.

Brain tumours and lymphoblastic leukemia that is acute are the most widespread cancer types in children but in Africa, lymphoma that is no-Hodgkin is the most widespread. The total number of children that are under the age of 15 that ended up being diagnosed with one type of cancer or the other in 2012 is around 165,000.

With an increase in age, it has been seen that the risk of getting cancer also increases significantly and the number and occurrence of cases of cancer in developed countries in more than the number and occurrence of cancer cases in other countries. The change in lifestyle and increase in the number of people living to a very old age in countries that are developing contributes to the increase in the rate of the occurrence of cancer. Cancer is believed to have a financial cost of up to 1.16 trillion dollars every year.

Cancer can be extremely dangerous when it is not discovered early and when adequate and proper care and attention is not given to the treatment. Therefore it is very important to go for regularly screening to find out if there is need for caution or treatment.

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To Live Until You Die: Palliative Care in Cancer Experience Essay (Article Review)

The end of life of the greater part of the patients can be characterized by their experience of distressing symptoms and the seriousness of the issue accounts for the importance and necessity of application of palliative care (American College of Physicians – American Society of Internal Medicine and End-of-Life Consensus Panel, 2001, p. 3). The same authors state that palliative care, the main focus of which is comfort and psychological support of the patient serves as the foundation for all health care (American College of Physicians – American Society of Internal Medicine and End-of-Life Consensus Panel, 2001, p. 3), which accounts for the importance of the present paper. The paper is devoted to the analysis of the two articles about end-of-life care in hospitals. However, the authors throw light on the common topic by applying different methodological approaches.

The analyzed article under the title “To Live Until You Die: Quality of Life at the End of Life” by Cramer (2010) is devoted to the issue of early introduction of palliative care in cancer experience (p. 53). In short and concise subsections, the author presents her opinion on the quality of life of patients, difficult conversations, presence, and communication as the necessary elements of palliative care. The author attributes the role of teachers to nurses; the idea of the article is that nurses can and should be the main effective bearers of palliative care.

Though the scientific foundation of the article cannot be questioned, and credibility of the material presented can be justified by the fact that the author is a clinical administrative supervisor at Tampa General Hospital and oncology, palliative care, critical care, and pediatric/neonatal educator at Real Nurse Ed in Tampa, FL. (Cramer, 2010, p. 55), the article can hardly be called the account of an experiment. It can rather be qualified as a motivation article aimed at nurses as the main administers of palliative care.

The greater part of the article is based on the professional experience of the author, the only experimental ground the author presents is “a prospective, longitudinal, multiple cohort studies of 332 patient and caregiver dyads” that studies the state of patients about the effectiveness of end-of-life discussions they are given (Cramer, 2010, p. 55). However, it is difficult to comment on the selection of participants, their experience, and the choice of data collection instruments since they are not mentioned by the researcher. Thus, additional information on the study is needed.

In contrast to the above-analyzed article, the second article under analysis, “End-of-life Care in Hospital: A Descriptive Study of All Inpatient Deaths in 1 Year.” by Abel and Rich, can be considered an investigation. The study was aimed at the quantitative assessment of the patients who died in a district general hospital in England while they could have been cared for at home; the researchers wanted to calculate the cost of each patient stay and to calculate the possible savings in hospital admissions (Abel and Rich, 2009, p. 616).

The authors have displayed sufficient control over all methodological components of the study. The choice of the participants (dead patients) accounts for the validity of the experiment. The authors explain the exclusion of patients below the age of 18, those who were not admitted to the hospital, and those who died in the Accident and Emergency Department (Abel and Rich, 2009, p. 617). The parameters of the assessment (primary diagnosis, reason of admission, etc.) account for the external validity of the experiment since the same parameters can be used in similar experiments in other hospitals (Grove, 2005, p. 219).

Concluding, it is possible to state that though both analyzed articles relate to end-of-life care, they cover different aspects of the issue. Thus, the first article cannot be qualified as the experiment as the account does not present the methodology, while the second article can be characterized as an account of the investigation and the validity and credibility of the study can be successfully proven.

Reference List

Abel, J., & Rich A. End-of-life Care in Hospital: A Descriptive Study of All Inpatient Deaths in 1 Year. (2009). Palliative Medicine , 23, 616-622.

American College of Physicians – American Society of Internal Medicine, & End-of-Life Care Consensus Panel. (2001). Physician’s Guide to End-of-Life Care . USA: ACP Press.

Cramer, C. (2010). To Live Until You Die: Quality of Life at the End of Life. Clinical Journal of Oncology Nursing, 14 (1), 53-56.

Grove, S.K. (2005). The Practice of Nursing Research: Conduct, Critique, and Utilization . USA: Elsevier Health Sciences.

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IvyPanda. (2022, June 7). To Live Until You Die: Palliative Care in Cancer Experience. https://ivypanda.com/essays/end-of-life-care-articles-analysis/

"To Live Until You Die: Palliative Care in Cancer Experience." IvyPanda , 7 June 2022, ivypanda.com/essays/end-of-life-care-articles-analysis/.

IvyPanda . (2022) 'To Live Until You Die: Palliative Care in Cancer Experience'. 7 June.

IvyPanda . 2022. "To Live Until You Die: Palliative Care in Cancer Experience." June 7, 2022. https://ivypanda.com/essays/end-of-life-care-articles-analysis/.

1. IvyPanda . "To Live Until You Die: Palliative Care in Cancer Experience." June 7, 2022. https://ivypanda.com/essays/end-of-life-care-articles-analysis/.

Bibliography

IvyPanda . "To Live Until You Die: Palliative Care in Cancer Experience." June 7, 2022. https://ivypanda.com/essays/end-of-life-care-articles-analysis/.

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Cancer Biology, Epidemiology, and Treatment in the 21st Century: Current Status and Future Challenges From a Biomedical Perspective

Patricia piña-sánchez.

1 Oncology Research Unit, Oncology Hospital, Mexican Institute of Social Security, Mexico

Antonieta Chávez-González

Martha ruiz-tachiquín, eduardo vadillo, alberto monroy-garcía, juan josé montesinos, rocío grajales.

2 Department of Medical Oncology, Oncology Hospital, Mexican Institute of Social Security, Mexico

Marcos Gutiérrez de la Barrera

3 Clinical Research Division, Oncology Hospital, Mexican Institute of Social Security, Mexico

Hector Mayani

Since the second half of the 20th century, our knowledge about the biology of cancer has made extraordinary progress. Today, we understand cancer at the genomic and epigenomic levels, and we have identified the cell that starts neoplastic transformation and characterized the mechanisms for the invasion of other tissues. This knowledge has allowed novel drugs to be designed that act on specific molecular targets, the immune system to be trained and manipulated to increase its efficiency, and ever more effective therapeutic strategies to be developed. Nevertheless, we are still far from winning the war against cancer, and thus biomedical research in oncology must continue to be a global priority. Likewise, there is a need to reduce unequal access to medical services and improve prevention programs, especially in countries with a low human development index.

Introduction

During the last one hundred years, our understanding of the biology of cancer increased in an extraordinary way. 1 - 4 Such a progress has been particularly prompted during the last few decades because of technological and conceptual progress in a variety of fields, including massive next-generation sequencing, inclusion of “omic” sciences, high-resolution microscopy, molecular immunology, flow cytometry, analysis and sequencing of individual cells, new cell culture techniques, and the development of animal models, among others. Nevertheless, there are many questions yet to be answered and many problems to be solved regarding this disease. As a consequence, oncological research must be considered imperative.

Currently, cancer is one of the illnesses that causes more deaths worldwide. 5 According to data reported in 2020 by the World Health Organization (WHO), cancer is the second cause of death throughout the world, with 10 million deaths. 6 Clearly, cancer is still a leading problem worldwide. With this in mind, the objective of this article is to present a multidisciplinary and comprehensive overview of the disease. We will begin by analyzing cancer as a process, focusing on the current state of our knowledge on 4 specific aspects of its biology. Then, we will look at cancer as a global health problem, considering some epidemiological aspects, and discussing treatment, with a special focus on novel therapies. Finally, we present our vision on some of the challenges and perspectives of cancer in the 21 st century.

The Biology of Cancer

Cancer is a disease that begins with genetic and epigenetic alterations occurring in specific cells, some of which can spread and migrate to other tissues. 4 Although the biological processes affected in carcinogenesis and the evolution of neoplasms are many and widely different, we will focus on 4 aspects that are particularly relevant in tumor biology: genomic and epigenomic alterations that lead to cell transformation, the cells where these changes occur, and the processes of invasion and metastasis that, to an important degree, determine tumor aggressiveness.

Cancer Genomics

The genomics of cancer can be defined as the study of the complete sequence of DNA and its expression in tumor cells. Evidently, this study only becomes meaningful when compared to normal cells. The sequencing of the human genome, completed in 2003, was not only groundbreaking with respect to the knowledge of our gene pool, but also changed the way we study cancer. In the post-genomic era, various worldwide endeavors, such as the Human Cancer Genome Project , the Cancer Genome ATLAS (TCGA), the International Cancer Genome Consortium, and the Pan-Cancer Analysis Working Group (PCAWG), have contributed to the characterization of thousands of primary tumors from different neoplasias, generating more than 2.5 petabytes (10 15 ) of genomic, epigenomic, and proteomic information. This has led to the building of databases and analytical tools that are available for the study of cancer from an “omic” perspective, 7 , 8 and it has helped to modify classification and treatment of various neoplasms.

Studies in the past decade, including the work by the PCAWG, have shown that cancer generally begins with a small number of driving mutations (4 or 5 mutations) in particular genes, including oncogenes and tumor-suppressor genes. Mutations in TP53, a tumor-suppressor gene, for example, are found in more than half of all cancer types as an early event, and they are a hallmark of precancerous lesions. 9 - 12 From that point on, the evolution of tumors may take decades, throughout which the mutational spectrum of tumor cells changes significantly. Mutational analysis of more than 19 000 exomes revealed a collection of genomic signatures, some associated with defects in the mechanism of DNA repair. These studies also revealed the importance of alterations in non-coding regions of DNA. Thus, for example, it has been observed that various pathways of cell proliferation and chromatin remodeling are altered by mutations in coding regions, while pathways, such as WNT and NOTCH, can be disrupted by coding and non-coding mutations. To the present date, 19 955 genes that codify for proteins and 25 511 genes for non-coding RNAs have been identified ( https://www.gencodegenes.org/human/stats.html ). Based on this genomic catalogue, the COSMIC (Catalogue Of Somatic Mutations In Cancer) repository, the most robust database to date, has registered 37 288 077 coding mutations, 19 396 fusions, 1 207 190 copy number variants, and 15 642 672 non-coding variants reported up to August 2020 (v92) ( https://cosmic-blog.sanger.ac.uk/cosmic-release-v92/ ).

The genomic approach has accelerated the development of new cancer drugs. Indeed, two of the most relevant initiatives in recent years are ATOM (Accelerating Therapeutics for Opportunities in Medicine), which groups industry, government and academia, with the objective of accelerating the identification of drugs, 13 and the Connectivity Map (CMAP), a collection of transcriptional data obtained from cell lines treated with drugs for the discovery of functional connections between genes, diseases, and drugs. The CMAP 1.0 covered 1300 small molecules and more than 6000 signatures; meanwhile, the CMAP 2.0 with L1000 assay profiled more than 1.3 million samples and approximately 400 000 signatures. 14

The genomic study of tumors has had 2 fundamental contributions. On the one hand, it has allowed the confirmation and expansion of the concept of intratumor heterogeneity 15 , 16 ; and on the other, it has given rise to new classification systems for cancer. Based on the molecular classification developed by expression profiles, together with mutational and epigenomic profiles, a variety of molecular signatures have been identified, leading to the production of various commercial multigene panels. In breast cancer, for example, different panels have been developed, such as Pam50/Prosigna , Blue Print , OncotypeDX , MammaPrint , Prosigna , Endopredict , Breast Cancer Index , Mammostrat, and IHC4 . 17

Currently, the genomic/molecular study of cancer is more closely integrated with clinical practice, from the classification of neoplasms, as in tumors of the nervous system, 18 to its use in prediction, as in breast cancer. 17 Improvement in molecular methods and techniques has allowed the use of smaller amounts of biological material, as well as paraffin-embedded samples for genomic studies, both of which provide a wealth of information. 19 In addition, non-invasive methods, such as liquid biopsies, represent a great opportunity not only for the diagnosis of cancer, but also for follow-up, especially for unresectable tumors. 20

Research for the production of genomic information on cancer is presently dominated by several consortia, which has allowed the generation of a great quantity of data. However, most of these consortia and studies are performed in countries with a high human development index (HDI), and countries with a low HDI are not well represented in these large genomic studies. This is why initiatives such as Human Heredity and Health in Africa (H3Africa) for genomic research in Africa are essential. 21 Generation of new information and technological developments, such as third-generation sequencing, will undoubtedly continue to move forward in a multidisciplinary and complex systems context. However, the existing disparities in access to genomic tools for diagnosis, prognosis, and treatment of cancer will continue to be a pressing challenge at regional and social levels.

Cancer Epigenetics

Epigenetics studies the molecular mechanisms that produce hereditable changes in gene expression, without causing alterations in the DNA sequence. Epigenetic events are of 3 types: methylation of DNA and RNA, histone modification (acetylation, methylation, and phosphorylation), and the expression of non-coding RNA. Epigenetic aberrations can drive carcinogenesis when they alter chromosome conformation and the access to transcriptional machinery and to various regulatory elements (promoters, enhancers, and anchors for interaction with chromatin, for example). These changes may activate oncogenesis and silence tumor-suppressor mechanisms when they modulate coding and non-coding sequences (such as micro-RNAs and long-RNAs). This can then lead to uncontrolled growth, as well as the invasion and metastasis of cancer cells.

While genetic mutations are stable and irreversible, epigenetic alterations are dynamic and reversible; that is, there are several epigenomes, determined by space and time, which cause heterogeneity of the “epigenetic status” of tumors during their development and make them susceptible to environmental stimuli or chemotherapeutic treatment. 22 Epigenomic variability creates differences between cells, and this creates the need to analyze cells at the individual level. In the past, epigenetic analyses measured “average states” of cell populations. These studies revealed general mechanisms, such as the role of epigenetic marks on active or repressed transcriptional states, and established maps of epigenetic composition in a variety of cell types in normal and cancerous tissue. However, these approaches are difficult to use to examine events occurring in heterogeneous cell populations or in uncommon cell types. This has led to the development of new techniques that permit marking of a sequence on the epigenome and improvement in the recovery yield of epigenetic material from individual cells. This has helped to determine changes in DNA, RNA, and histones, chromatin accessibility, and chromosome conformation in a variety of neoplasms. 23 , 24

In cancer, DNA hypomethylation occurs on a global scale, while hypermethylation occurs in specific genomic loci, associated with abnormal nucleosome positioning and chromatin modifications. This information has allowed epigenomic profiles to be established in different types of neoplasms. In turn, these profiles have served as the basis to identify new neoplasm subgroups. For example, in triple negative breast cancer (TNBC), 25 and in hepatocellular carcinoma, 26 DNA methylation profiles have helped to the identification of distinct subgroups with clinical relevance. Epigenetic approaches have also helped to the development of prognostic tests to assess the sensitivity of cancer cells to specific drugs. 27

Epigenetic traits could be used to characterize intratumoral heterogeneity and determine the relevance of such a heterogeneity in clonal evolution and sensitivity to drugs. However, it is clear that heterogeneity is not only determined by genetic and epigenetic diversity resulting from clonal evolution of tumor cells, but also by the various cell populations that form the tumor microenvironment (TME). 28 Consequently, the epigenome of cancer cells is continually remodeled throughout tumorigenesis, during resistance to the activity of drugs, and in metastasis. 29 This makes therapeutic action based on epigenomic profiles difficult, although significant advances in this area have been reported. 30

During carcinogenesis and tumor progression, epigenetic modifications are categorized by their mechanisms of regulation ( Figure 1A ) and the various levels of structural complexity ( Figure 1B ). In addition, the epigenome can be modified by environmental stimuli, stochastic events, and genetic variations that impact the phenotype ( Figure 1C ). 31 , 32 The molecules that take part in these mechanisms/events/variations are therapeutic targets of interest with potential impact on clinical practice. There are studies on a wide variety of epidrugs, either alone or in combination, which improve antitumor efficacy. 33 However, the problems with these drugs must not be underestimated. For a considerable number of epigenetic compounds still being under study, the main challenge is to translate in vitro efficacy of nanomolar (nM) concentrations into well-tolerated and efficient clinical use. 34 The mechanisms of action of epidrugs may not be sufficiently controlled and could lead to diversion of the therapeutic target. 35 It is known that certain epidrugs, such as valproic acid, produce unwanted epigenetic changes 36 ; thus the need for a well-established safety profile before these drugs can be used in clinical therapy. Finally, resistance to certain epidrugs is another relevant problem. 37 , 38

Epigenetics of cancer. (A) Molecular mechanisms. (B) Structural hierarchy of epigenomics. (C) Factors affecting the epigenome. Modified from Refs. 31 and 32 .

As we learn about the epigenome of specific cell populations in cancer patients, a door opens to the evaluation of sensitivity tests and the search for new molecular markers for detection, prognosis, follow-up, and/or response to treatment at various levels of molecular regulation. Likewise, the horizon expands for therapeutic alternatives in oncology with the use of epidrugs, such as pharmacoepigenomic modulators for genes and key pathways, including methylation of promoters and regulation of micro-RNAs involved in chemoresponse and immune response in cancer. 39 There is no doubt that integrated approaches identifying stable pharmagenomic and epigenomic patterns and their relation with expression profiles and genetic functions will be more and more valuable in our fight against cancer.

Cancer Stem Cells

Tumors consist of different populations of neoplastic cells and a variety of elements that form part of the TME, including stromal cells and molecules of the extracellular matrix. 40 Such intratumoral heterogeneity becomes even more complex during clonal variation of transformed cells, as well as influence the elements of the TME have on these cells throughout specific times and places. 41 To explain the origin of cancer cell heterogeneity, 2 models have been put forward. The first proposes that mutations occur at random during development of the tumor in individual neoplastic cells, and this promotes the production of various tumor populations, which acquire specific growth and survival traits that lead them to evolve according to intratumor mechanisms of natural selection. 42 The second model proposes that each tumor begins as a single cell that possess 2 functional properties: it can self-renew and it can produce several types of terminal cells. As these 2 properties are characteristics of somatic stem cells, 43 the cells have been called cancer stem cells (CSCs). 44 According to this model, tumors must have a hierarchical organization, where self-renewing stem cells produce highly proliferating progenitor cells, unable to self-renew but with a high proliferation potential. The latter, in turn, give rise to terminal cells. 45 Current evidence indicates that both models may coexist in tumor progression. In agreement with this idea, new subclones could be produced as a result of a lack of genetic stability and mutational changes, in addition to the heterogeneity derived from the initial CSC and its descendants. Thus, in each tumor, a set of neoplastic cells with different genetic and epigenetic traits may be found, which would provide different phenotypic properties. 46

The CSC concept was originally presented in a model of acute myeloid leukemia. 47 The presence of CSCs was later proved in chronic myeloid leukemia, breast cancer, tumors of the central nervous system, lung cancer, colon cancer, liver cancer, prostate cancer, pancreatic cancer, melanoma, and cancer of the head and neck, amongst others. In all of these cases, detection of CSCs was based on separation of several cell populations according to expression of specific surface markers, such as CD133, CD44, CD24, CD117, and CD15. 48 It is noteworthy that in some solid tumors, and even in some hematopoietic ones, a combination of specific markers that allow the isolation of CSCs has not been found. Interestingly, in such tumors, a high percentage of cells with the capacity to start secondary tumors has been observed; thus, the terms Tumor Initiating Cells (TIC) or Leukemia Initiating Cells (LIC) have been adopted. 46

A relevant aspect of the biology of CSCs is that, just like normal stem cells, they can self-renew. Such self-renewal guarantees the maintenance or expansion of the tumor stem cell population. Another trait CSCs share with normal stem cells is their quiescence, first described in chronic myeloid leukemia. 49 The persistence of quiescent CSCs in solid tumors has been recently described in colorectal cancer, where quiescent clones can become dominant after therapy with oxaliplatin. 50 In non-hierarchical tumors, such as melanoma, the existence of slow-cycling cells that are resistant to antimitogenic agents has also been proved. 51 Such experimental evidence supports the idea that quiescent CSCs or TICs are responsible for both tumor resistance to antineoplastic drugs and clinical relapse after initial therapeutic success.

In addition to quiescence, CSCs use other mechanisms to resist the action of chemotherapeutic drugs. One of these is their increased numbers: upon diagnosis, a high number of CSCs are observed in most analyzed tumors, making treatment unable to destroy all of them. On the other hand, CSCs have a high number of molecular pumps that expulse drugs, as well as high numbers of antiapoptotic molecules. In addition, they have very efficient mechanisms to repair DNA damage. In general, these cells show changes in a variety of signaling pathways involved in proliferation, survival, differentiation, and self-renewal. It is worth highlighting that in recent years, many of these pathways have become potential therapeutic targets in the elimination of CSCs. 52 Another aspect that is highly relevant in understanding the biological behavior of CSCs is that they require a specific site for their development within the tissue where they are found that can provide whatever is needed for their survival and growth. These sites, known as niches, are made of various cells, both tumor and non-tumor, as well as a variety of non-cellular elements (extracellular matrix [ECM], soluble cytokines, ion concentration gradients, etc.), capable of regulating the physiology of CSCs in order to promote their expansion, the invasion of adjacent tissues, and metastasis. 53

It is important to consider that although a large number of surface markers have been identified that allow us to enrich and prospectively follow tumor stem cell populations, to this day there is no combination of markers that allows us to find these populations in all tumors, and it is yet unclear if all tumors present them. In this regard, it is necessary to develop new purification strategies based on the gene expression profiles of these cells, so that tumor heterogeneity is taken into account, as it is evident that a tumor can include multiple clones of CSCs that, in spite of being functional, are genetically different, and that these clones can vary throughout space (occupying different microenvironments and niches) and time (during the progression of a range of tumor stages). Such strategies, in addition to new in vitro and in vivo assays, will allow the development of new and improved CSC elimination strategies. This will certainly have an impact on the development of more efficient therapeutic alternatives.

Invasion and Metastasis

Nearly 90% of the mortality associated with cancer is related to metastasis. 54 This consists of a cascade of events ( Figure 2 ) that begins with the local invasion of a tumor into surrounding tissues, followed by intravasation of tumor cells into the blood stream or lymphatic circulation. Extravasation of neoplastic cells in areas distant from the primary tumor then leads to the formation of one or more micrometastatic lesions which subsequently proliferate to form clinically detectable lesions. 4 The cells that are able to produce metastasis must acquire migratory characteristics, which occur by a process known as epithelial–mesenchymal transition (EMT), that is, the partial loss of epithelial characteristics and the acquirement of mesenchymal traits. 55

Invasion and metastasis cascade. Invasion and metastasis can occur early or late during tumor progression. In either case, invasion to adjacent tissues is driven by stem-like cells (cancer stem cells) that acquire the epithelial–mesenchymal transition (EMT) (1). Once they reach sites adjacent to blood vessels, tumor cells (individually or in clusters) enter the blood (2). Tumor cells in circulation can adhere to endothelium and extravasation takes place (3). Other mechanisms alternative to extravasation can exist, such as angiopelosis, in which clusters of tumor cells are internalized by the endothelium. Furthermore, at certain sites, tumor cells can obstruct microvasculature and initiate a metastatic lesion right there. Sometimes, a tumor cells that has just exit circulation goes into an MET in order to become quiescent (4). Inflammatory signals can activate quiescent metastatic cells that will proliferate and generate a clinically detectable lesion (5).

Although several of the factors involved in this process are currently known, many issues are still unsolved. For instance, it has not yet been possible to monitor in vivo the specific moment when it occurs 54 ; the microenvironmental factors of the primary tumor that promote such a transition are not known with precision; and the exact moment during tumor evolution in which one cell or a cluster of cells begin to migrate to distant areas, is also unknown. The wide range of possibilities offered by intra- and inter-tumoral heterogeneity 56 stands in the way of suggesting a generalized strategy that could resolve this complication.

It was previously believed that metastasis was only produced in late stages of tumor progression; however, recent studies indicate that EMT and metastasis can occur during the early course of the disease. In pancreatic cancer, for example, cells going through EMT are able to colonize and form metastatic lesions in the liver in the first stages of the disease. 52 , 57 Metastatic cell clusters circulating in peripheral blood (PB) are prone to generate a metastatic site, compared to individual tumor cells. 58 , 59 In this regard, novel strategies, such as the use of micro-RNAs, are being assessed in order to diminish induction of EMT. 60 It must be mentioned, however, that the metastatic process seems to be even more complex, with alternative pathways that do not involve EMT. 61 , 62

A crucial stage in the process of metastasis is the intravasation of tumor cells (alone or in clusters) towards the blood stream and/or lymphatic circulation. 63 These mechanisms are also under intensive research because blocking them could allow the control of spreading of the primary tumor. In PB or lymphatic circulation, tumor cells travel to distant parts for the potential formation of a metastatic lesion. During their journey, these cells must stand the pressure of blood flow and escape interaction with natural killer (NK) cells . 64 To avoid them, tumor cells often cover themselves with thrombocytes and also produce factors such as VEGF, angiopoietin-2, angiopoietin-4, and CCL2 that are involved in the induction of vascular permeability. 54 , 65 Neutrophils also contribute to lung metastasis in the bloodstream by secreting IL-1β and metalloproteases to facilitate extravasation of tumor cells. 64

The next step in the process of metastasis is extravasation, for which tumor cells, alone or in clusters, can use various mechanisms, including a recently described process known as angiopellosis that involves restructuring the endothelial barrier to internalize one or several cells into a tissue. 66 The study of leukocyte extravasation has contributed to a more detailed knowledge of this process, in such a way that some of the proposed strategies to avoid extravasation include the use of integrin inhibitors, molecules that are vital for rolling, adhesion, and extravasation of tumor cells. 67 , 68 Another strategy that has therapeutic potential is the use of antibodies that strengthen vascular integrity to obstruct transendothelial migration of tumor cells and aid in their destruction in PB. 69

Following extravasation, tumor cells can return to an epithelial phenotype, a process known as mesenchymal–epithelial transition and may remain inactive for several years. They do this by competing for specialized niches, like those in the bone marrow, brain, and intestinal mucosa, which provide signals through the Notch and Wnt pathways. 70 Through the action of the Wnt pathway, tumor cells enter a slow state of the cell cycle and induce the expression of molecules that inhibit the cytotoxic function of NK cells. 71 The extravasated tumor cell that is in a quiescent state must comply with 2 traits typical of stem cells: they must have the capacity to self-renew and to generate all of the cells that form the secondary tumor.

There are still several questions regarding the metastatic process. One of the persisting debates at present is if EMT is essential for metastasis or if it plays a more important role in chemoresistance. 61 , 62 It is equally important to know if there is a pattern in each tumor for the production of cells with the capacity to carry out EMT. In order to control metastasis, it is fundamental to know what triggers acquisition of the migratory phenotype and the intrinsic factors determining this transition. Furthermore, it is essential to know if mutations associated with the primary tumor or the variety of epigenetic changes are involved in this process. 55 It is clear that metastatic cells have affinity for certain tissues, depending on the nature of the primary tumor (seed and soil hypothesis). This may be caused by factors such as the location and the direction of the bloodstream or lymphatic fluid, but also by conditioning of premetastatic niches at a distance (due to the large number of soluble factors secreted by the tumor and the recruitment of cells of the immune system to those sites). 72 We have yet to identify and characterize all of the elements that participate in this process. Deciphering them will be of upmost importance from a therapeutic point of view.

Epidemiology of Cancer

Cancer is the second cause of death worldwide; today one of every 6 deaths is due to a type of cancer. According to the International Agency for Research on Cancer (IARC), in 2020 there were approximately 19.3 million new cases of cancer, and 10 million deaths by this disease, 6 while 23.8 million cases and 13.0 million deaths are projected to occur by 2030. 73 In this regard, it is clear the increasing role that environmental factors—including environmental pollutants and processed food—play as cancer inducers and promoters. 74 The types of cancer that produce the greatest numbers of cases and deaths worldwide are indicated in Table 1 . 6

Total Numbers of Cancer Cases and Deaths Worldwide in 2020 by Cancer Type (According to the Global Cancer Observatory, IARC).

Data presented on this table were obtained from Ref. 6.

As shown in Figure 3 , lung, breast, prostate, and colorectal cancer are the most common throughout the world, and they are mostly concentrated in countries of high to very high human development index (HDI). Although breast, prostate, and colorectal cancer have a high incidence, the number of deaths they cause is proportionally low, mostly reflecting the great progress made in their control. However, these data also reveal the types of cancer that require further effort in prevention, precise early detection avoiding overdiagnosis, and efficient treatment. This is the case of liver, lung, esophageal, and pancreatic cancer, where the difference between the number of cases and deaths is smaller ( Figure 3B ). Social and economic transition in several countries has had an impact on reducing the incidence of neoplasms associated with infection and simultaneously produced an increase in the types related to reproductive, dietary, and hormonal factors. 75

Incidence and mortality for some types of cancer in the world. (A) Estimated number of cases and deaths in 2020 for the most frequent cancer types worldwide. (B) Incidence and mortality rates, normalized according to age, for the most frequent cancer types in countries with very high/& high (VH&H; blue) and/low and middle (L&M; red) Human Development Index (HDI). Data include both genders and all ages. Data according to https://gco.iarc.fr/today , as of June 10, 2021.

In the past 3 decades, cancer mortality rates have fallen in high HDI countries, with the exception of pancreatic cancer, and lung cancer in women. Nevertheless, changes in the incidence of cancer do not show the same consistency, possibly due to variables such as the possibility of early detection, exposure to risk factors, or genetic predisposition. 76 , 77 Countries such as Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the United Kingdom have reported a reduction in incidence and mortality in cancer of the stomach, colon, lung, and ovary, as well as an increase in survival. 78 Changes in modifiable risk factors, such as the use of tobacco, have played an important role in prevention. In this respect, it has been estimated that decline in tobacco use can explain between 35% and 45% of the reduction in cancer mortality rates, 79 while the fall in incidence and mortality due to stomach cancer can be attributed partly to the control of Helicobacter pylori infection. 80 Another key factor in the fall of mortality rates in developed countries has been an increase in early detection as a result of screening programs, as in breast and prostate cancer, which have had their mortality rates decreased dramatically in spite of an increase in their incidence. 76

Another important improvement observed in recent decades is the increase in survival rates, particularly in high HDI countries. In the USA, for example, survival rates for patients with prostate cancer at 5 years after initial diagnosis was 28% during 1947–1951; 69% during 1975–1977, and 100% during 2003–2009. Something similar occurred with breast cancer, with a 5-year survival rate of 54% in 1947–1951, 75% in 1975–1977, and 90% in 2003–2009. 81 In the CONCORD 3 version, age-standardize 5-year survival for patients with breast cancer in the USA during 2010–2014 was 90%, and 97% for prostate cancer patients. 82 Importantly, even among high HDI countries, significant differences have been identified in survival rates, being stage of disease at diagnosis, time for access to effective treatment, and comorbidities, the main factors influencing survival in these nations. 78 Unfortunately, survival rates in low HDI countries are significantly lower due to several factors, including lack of information, deficient screening and early detection programs, limited access to treatment, and suboptimal cancer registration. 82 It should be noted that in countries with low to middle HDI, neoplasms with the greatest incidence are those affecting women (breast and cervical cancer), which reflects not only a problem with access to health services, but also a serious inequality issue that involves social, cultural, and even religious obstacles. 83

Up to 42% of incident cases and 47% of deaths by cancer in the USA are due to potentially modifiable risk factors such as use of tobacco, physical activity, diet, and infection. 84 It has been calculated that 2.4 million deaths by cancer, mostly of the lung, can be attributed to tobacco. 73 In 2020, the incidence rate of lung cancer in Western Africa was 2.2, whereas in Polynesia and Eastern Asia was 37.3 and 34.4, respectively. 6 In contrast, the global burden of cancer associated with infection was 15.4%, but in Sub-Saharan Africa it was 30%. 85 Likewise, the incidence of cervical cancer in Eastern Africa was 40.1, in contrast with the USA and Canada that have a rate of 6.2. This makes it clear that one of the challenges we face is the reduction of the risk factors that are potentially modifiable and associated with specific types of cancer.

Improvement of survival rates and its disparities worldwide are also important challenges. Five-year survival for breast cancer—diagnosed during 2010-2014— in the USA, for example, was 90%, whereas in countries like South Africa it was 40%. 82 Childhood leukemia in the USA and several European countries shows a 5-year survival of 90%, while in Latin-American countries it is 50–76%. 86 Interestingly, there are neoplasms, such as pancreatic cancer, for which there has been no significant increase in survival, which remains low (5–15%) both in developed and developing countries. 82

Although data reported on global incidence and mortality gives a general overview on the epidemiology of cancer, it is important to note that there are great differences in coverage of cancer registries worldwide. To date, only 1 out of every 3 countries reports high quality data on the incidence of cancer. 87 For the past 50 years, the IARC has supported population-based cancer registries; however, more than one-third of the countries belonging to the WHO, mainly countries of low and middle income (LMIC), have no data on more than half of the 18 indicators of sustainable development goals. 88 High quality cancer registries only cover 4% of the population in Africa, 8% in Asia, and 7% in Latin America, contrasting with 83% in the USA and Canada, and 33% in Europe. 89 In response to this situation, the Global Initiative for Cancer Registry Development was created in 2012 to generate improved infrastructure to permit greater coverage and better quality registries, especially in countries with low and middle HDI. 88 It is expected that initiatives of this sort in the coming years will allow more and better information to guide strategies for the control of cancer worldwide, especially in developing regions. This will enable survival to be measured over longer periods of time (10, 15, or 20 years), as an effective measure in the control of cancer. The WHO has established as a target for 2025 to reduce deaths by cancer and other non-transmissible diseases by 25% in the population between the ages of 30–69; such an effort requires not only effective prevention measures to reduce incidence, but also more efficient health systems to diminish mortality and increase survival. At the moment, it is an even greater challenge because of the effects of the COVID-19 pandemic which has negatively impacted cancer prevention and health services. 90

Oncologic Treatments

A general perspective.

At the beginning of the 20th century, cancer treatment, specifically treatment of solid tumors, was based fundamentally on surgical resection of tumors, which together with other methods for local control, such as cauterization, had been used since ancient times. 91 At that time, there was an ongoing burst of clinical observations along with interventions sustained on fundamental knowledge about physics, chemistry, and biology. In the final years of the 19 th century and the first half of the 20th, these technological developments gave rise to radiotherapy, hormone therapy, and chemotherapy. 92 - 94 Simultaneously, immunotherapy was also developed, although usually on a smaller scale, in light of the overwhelming progress of chemotherapy and radiotherapy. 95

Thus began the development and expansion of disciplines based on these approaches (surgery, radiotherapy, chemotherapy, hormone therapy, and immunotherapy), with their application evolving ever more rapidly up to their current uses. Today, there is a wide range of therapeutic tools for the care of cancer patients. These include elements that emerged empirically, arising from observations of their effects in various medical fields, as well as drugs that were designed to block processes and pathways that form part of the physiopathology of one or more neoplasms according to knowledge of specific molecular alterations. A classic example of the first sort of tool is mustard gas, originally used as a weapon in war, 96 but when applied for medical purposes, marked the beginning of the use of chemicals in the treatment of malignant neoplasms, that is, chemotherapy. 94 A clear example of the second case is imatinib, designed specifically to selectively inhibit a molecular alteration in chronic myeloid leukemia: the Bcr-Abl oncoprotein. 97

It is on this foundation that today the 5 areas mentioned previously coexist and complement one another. The general framework that motivates this amalgam and guides its development is precision medicine, founded on the interaction of basic and clinical science. In the forecasts for development in each of these fields, surgery is expected to continue to be the fundamental approach for primary tumors in the foreseeable future, as well as when neoplastic disease in the patient is limited, or can be limited by applying systemic or regional elements, before and/or after surgical resection, and it can be reasonably anticipated for the patient to have a significant period free from disease or even to be cured. With regards to technology, intensive exploration of robotic surgery is contemplated. 98

The technological possibilities for radiotherapy have progressed in such a way that it is now possible to radiate neoplastic tissue with an extraordinary level of precision, and therefore avoid damage to healthy tissue. 99 This allows administration of large doses of ionizing radiation in one or a few fractions, what is known as “radiosurgery.” The greatest challenges to the efficacy of this approach are related to radio-resistance in certain neoplasms. Most efforts regarding research in this field are concentrated on understanding the underlying biological mechanisms of the phenomenon and their potential control through radiosensitizers. 100

“Traditional” chemotherapy, based on the use of compounds obtained from plants and other natural products, acting in a non-specific manner on both neoplastic and healthy tissues with a high proliferation rate, continues to prevail. 101 The family of chemotherapeutic drugs currently includes alkylating agents, antimetabolites, anti-topoisomerase agents, and anti-microtubules. Within the pharmacologic perspective, the objective is to attain a high concentration or activity of such molecules in specific tissues while avoiding their accumulation in others, in order to achieve an increase in effectiveness and a reduction in toxicity. This has been possible with the use of viral vectors, for example, that are able to limit their replication in neoplastic tissues, and activate prodrugs of normally nonspecific agents, like cyclophosphamide, exclusively in those specific areas. 102 More broadly, chemotherapy also includes a subgroup of substances, known as molecular targeted therapy, that affect processes in a more direct and specific manner, which will be mentioned later.

There is no doubt that immunotherapy—to be explored next—is one of the therapeutic fields where development has been greatest in recent decades and one that has produced enormous expectation in cancer treatment. 103 Likewise, cell therapy, based on the use of immune cells or stem cells, has come to complement the oncologic therapeutic arsenal. 43 Each and every one of the therapeutic fields that have arisen in oncology to this day continue to prevail and evolve. Interestingly, the foreseeable future for the development of cancer treatment contemplates these approaches in a joint and complementary manner, within the general framework of precision medicine, 104 and sustained by knowledge of the biological mechanisms involved in the appearance and progression of neoplasms. 105 , 106

Immunotherapy

Stimulating the immune system to treat cancer patients has been a historical objective in the field of oncology. Since the early work of William Coley 107 to the achievements reached at the end of the 20 th century, scientific findings and technological developments paved the way to searching for new immunotherapeutic strategies. Recombinant DNA technology allowed the synthesis of cytokines, such as interferon-alpha (IFN-α) and interleukin 2 (IL-2), which were authorized by the US Food and Drug Administration (FDA) for the treatment of hairy cell leukemia in 1986, 108 as well as kidney cancer and metastatic melanoma in 1992 and 1998, respectively. 109

The first therapeutic vaccine against cancer, based on the use of autologous dendritic cells (DCs), was approved by the FDA against prostate cancer in 2010. However, progress in the field of immunotherapy against cancer was stalled in the first decade of the present century, mostly due to failure of several vaccines in clinical trials. In many cases, application of these vaccines was detained by the complexity and cost involved in their production. Nevertheless, with the coming of the concept of immune checkpoint control, and the demonstration of the relevance of molecules such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), and programmed cell death molecule-1 (PD-1), immunotherapy against cancer recovered its global relevance. In 2011, the monoclonal antibody (mAb) ipilimumab, specific to the CTLA-4 molecule, was the first checkpoint inhibitor (CPI) approved for the treatment of advanced melanoma. 110 Later, inhibitory mAbs for PD-1, or for the PD-1 ligand (PD-L1), 111 as well as the production of T cells with chimeric receptors for antigen recognition (CAR-T), 112 which have been approved to treat various types of cancer, including melanoma, non-small cell lung cancer (NSCLC), head and neck cancer, bladder cancer, renal cell carcinoma (RCC), and hepatocellular carcinoma, among others, have changed the paradigm of cancer treatment.

In spite of the current use of anti-CTLA-4 and anti-PD-L1 mAbs, only a subgroup of patients has responded favorably to these CPIs, and the number of patients achieving clinical benefit is still small. It has been estimated that more than 70% of patients with solid tumors do not respond to CPI immunotherapy because either they show primary resistance, or after responding favorably, develop resistance to treatment. 113 In this regard, it is important to mention that in recent years very important steps have been taken to identify the intrinsic and extrinsic mechanisms that mediate resistance to CPI immunotherapy. 114 Intrinsic mechanisms include changes in the antitumor immune response pathways, such as faulty processing and presentation of antigens by APCs, activation of T cells for tumor cell destruction, and changes in tumor cells that lead to an immunosuppressive TME. Extrinsic factors include the presence of immunosuppressive cells in the local TME, such as regulatory T cells, myeloid-derived suppressor cells (MDSC), mesenchymal stem/stromal cells (MSCs), and type 2 macrophages (M2), in addition to immunosuppressive cytokines.

On the other hand, classification of solid tumors as “hot,” “cold,” or “excluded,” depending on T cell infiltrates and the contact of such infiltrates with tumor cells, as well as those that present high tumor mutation burden (TMB), have redirected immunotherapy towards 3 main strategies 115 ( Table 2 ): (1) Making T-cell antitumor response more effective, using checkpoint inhibitors complementary to anti-CTLA-4 and anti-PD-L1, such as LAG3, Tim-3, and TIGT, as well as using CAR-T cells against tumor antigens. (2) Activating tumor-associated myeloid cells including monocytes, granulocytes, macrophages, and DC lineages, found at several frequencies within human solid tumors. (3) Regulating the biochemical pathways in TME that produce high concentrations of immunosuppressive molecules, such as kynurenine, a product of tryptophan metabolism, through the activity of indoleamine 2,3 dioxygenase; or adenosine, a product of ATP hydrolysis by the activity of the enzyme 5’nucleotidase (CD73). 116

Current Strategies to Stimulate the Immune Response for Antitumor Immunotherapy.

Abbreviations: TME, tumor microenvironment; IL, interleukin; TNF, Tumor Necrosis Factor; TNFR, TNF-receptor; CD137, receptor–co-stimulator of the TNFR family; OX40, member number 4 of the TNFR superfamily; CD27/CD70, member of the TNFR superfamily; CD40/CD40L, antigen-presenting cells (APC) co-stimulator and its ligand; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; STING, IFN genes-stimulator; RIG-I, retinoic acid inducible gene-I; MDA5, melanoma differentiation-associated protein 5; CDN, cyclic dinucleotide; ATP, adenosine triphosphate; HMGB1, high mobility group B1 protein; TLR, Toll-like receptor; HVEM, Herpes virus entry mediator; GITR, glucocorticoid-induced TNFR family-related gene; CTLA4, cytotoxic T lymphocyte antigen 4; PD-L1, programmed death ligand-1; TIGIT, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibition motives; CSF1/CSF1R, colony-stimulating factor-1 and its receptor; CCR2, Type 2 chemokine receptor; PI3Kγ, Phosphoinositide 3-Kinase γ; CXCL/CCL, chemokine ligands; LFA1, lymphocyte function-associated antigen 1; ICAM1, intercellular adhesion molecule 1; VEGF, vascular endothelial growth factor; IDO, indolamine 2,3-dioxigenase; TGF, transforming growth factor; LAG-3, lymphocyte-activation gene 3 protein; TIM-3, T-cell immunoglobulin and mucin-domain containing-3; CD73, 5´nucleotidase; ARs, adenosine receptors; Selectins, cell adhesion molecules; CAR-T, chimeric antigen receptor T cell; TCR-T, T-cell receptor engineered T cell.

Apart from the problems associated with its efficacy (only a small group of patients respond to it), immunotherapy faces several challenges related to its safety. In other words, immunotherapy can induce adverse events in patients, such as autoimmunity, where healthy tissues are attacked, or cytokine release syndrome and vascular leak syndrome, as observed with the use of IL-2, both of which lead to serious hypotension, fever, renal failure, and other adverse events that are potentially lethal. The main challenges to be faced by immunotherapy in the future will require the combined efforts of basic and clinical scientists, with the objective of accelerating the understanding of the complex interactions between cancer and the immune system, and improve treatment options for patients. Better comprehension of immune phenotypes in tumors, beyond the state of PD-L1 and TME, will be relevant to increase immunotherapy efficacy. In this context, the identification of precise tumor antigenicity biomarkers by means of new technologies, such as complete genome sequencing, single cell sequencing, and epigenetic analysis to identify sites or subclones typical in drug resistance, as well as activation, traffic and infiltration of effector cells of the immune response, and regulation of TME mechanisms, may help define patient populations that are good candidates for specific therapies and therapeutic combinations. 117 , 118 Likewise, the use of agents that can induce specific activation and modulation of the response of T cells in tumor tissue, will help improve efficacy and safety profiles that can lead to better clinical results.

Molecular Targeted Therapy

For over 30 years, and based on the progress in our knowledge of tumor biology and its mechanisms, there has been a search for therapeutic alternatives that would allow spread and growth of tumors to be slowed down by blocking specific molecules. This approach is known as molecular targeted therapy. 119 Among the elements generally used as molecular targets there are transcription factors, cytokines, membrane receptors, molecules involved in a variety of signaling pathways, apoptosis modulators, promoters of angiogenesis, and cell cycle regulators. 120

Imatinib, a tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia, became the first targeted therapy in the final years of the 1990s. 97 From then on, new drugs have been developed by design, and today more than 60 targeted therapies have been approved by the FDA for the treatment of a variety of cancers ( Table 3 ). 121 This has had a significant impact on progression-free survival and global survival in neoplasms such as non-small cell lung cancer, breast cancer, renal cancer, and melanoma.

FDA Approved Molecular Targeted Therapies for the Treatment of Solid Tumors.

Abbreviations: mAb, monoclonal antibody; ALK, anaplastic lymphoma kinase; CDK, cyclin-dependent kinase; CTLA-4, cytotoxic lymphocyte antigen-4; EGFR, epidermal growth factor receptor; FGFR, fibroblast growth factor receptor; GIST, gastrointestinal stroma tumor; mTOR, target of rapamycine in mammal cells; NSCLC, non-small cell lung carcinoma; PARP, poli (ADP-ribose) polimerase; PD-1, programmed death protein-1; PDGFR, platelet-derived growth factor receptor; PD-L1, programmed death ligand-1; ER, estrogen receptor; PR, progesterone receptor; TKR, tyrosine kinase receptors; SERM, selective estrogen receptor modulator; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor. Modified from Ref. [ 127 ].

Most drugs classified as targeted therapies form part of 2 large groups: small molecules and mAbs. The former are defined as compounds of low molecular weight (<900 Daltons) that act upon entering the cell. 120 Targets of these compounds are cell cycle regulatory proteins, proapoptotic proteins, or DNA repair proteins. These drugs are indicated based on histological diagnosis, as well as molecular tests. In this group there are multi-kinase inhibitors (RTKs) and tyrosine kinase inhibitors (TKIs), like sunitinib, sorafenib, and imatinib; cyclin-dependent kinase (CDK) inhibitors, such as palbociclib, ribociclib and abemaciclib; poli (ADP-ribose) polimerase inhibitors (PARPs), like olaparib and talazoparib; and selective small-molecule inhibitors, like ALK and ROS1. 122

As for mAbs, they are protein molecules that act on membrane receptors or extracellular proteins by interrupting the interaction between ligands and receptors, in such a way that they reduce cell replication and induce cytostasis. Among the most widely used mAbs in oncology we have: trastuzumab, a drug directed against the receptor for human epidermal growth factor-2 (HER2), which is overexpressed in a subgroup of patients with breast and gastric cancer; and bevacizumab, that blocks vascular endothelial growth factor and is used in patients with colorectal cancer, cervical cancer, and ovarian cancer. Other mAbs approved by the FDA include pembolizumab, atezolizumab, nivolumab, avelumab, ipilimumab, durvalumab, and cemiplimab. These drugs require expression of response biomarkers, such as PD-1 and PD-L1, and must also have several resistance biomarkers, such as the expression of EGFR, the loss of PTEN, and alterations in beta-catenin. 123

Because cancer is such a diverse disease, it is fundamental to have precise diagnostic methods that allow us to identify the most adequate therapy. Currently, basic immunohistochemistry is complemented with neoplastic molecular profiles to determine a more accurate diagnosis, and it is probable that in the near future cancer treatments will be based exclusively on molecular profiles. In this regard, it is worth mentioning that the use of targeted therapy depends on the existence of specific biomarkers that indicate if the patient will be susceptible to the effects of the drug or not. Thus, the importance of underlining that not all patients are susceptible to receive targeted therapy. In certain neoplasms, therapeutic targets are expressed in less than 5% of the diagnosed population, hindering a more extended use of certain drugs.

The identification of biomarkers and the use of new generation sequencing on tumor cells has shown predictive and prognostic relevance. Likewise, mutation analysis has allowed monitoring of tumor clone evolution, providing information on changes in canonic gene sequences, such as TP53, GATA3, PIK3CA, AKT1, and ERBB2; infrequent somatic mutations developed after primary treatments, like SWI-SNF and JAK2-STAT3; or acquired drug resistance mutations such as ESR1. 124 The study of mutations is vital; in fact, many of them already have specific therapeutic indications, which have helped select adequate treatments. 125

There is no doubt that molecular targeted therapy is one of the main pillars of precision medicine. However, it faces significant problems that often hinder obtaining better results. Among these, there is intratumor heterogeneity and differences between the primary tumor and metastatic sites, as well as intrinsic and acquired resistance to these therapies, the mechanisms of which include the presence of heterogeneous subclones, DNA hypermethylation, histone acetylation, and interruption of mRNA degradation and translation processes. 126 Nonetheless, beyond the obstacles facing molecular targeted therapy from a biological and methodological point of view, in the real world, access to genomic testing and specific drugs continues to be an enormous limitation, in such a way that strategies must be designed in the future for precision medicine to be possible on a global scale.

Cell Therapy

Another improvement in cancer treatment is the use of cell therapy, that is, the use of specific cells as therapeutic agents. This clinical procedure has 2 modalities: the first consists of replacing and regenerating functional cells in a specific tissue by means of stem/progenitor cells of a certain kind, 43 while the second uses immune cells as effectors to eliminate malignant cells. 127

Regarding the first type, we must emphasize the development of cell therapy based on hematopoietic stem and progenitor cells. 128 For over 50 years, hematopoietic cell transplants have been used to treat a variety of hematologic neoplasms (different forms of leukemia and lymphoma). Today, it is one of the most successful examples of cell therapy, including innovative modalities, such as haploidentical transplants, 129 as well as application of stem cells expanded ex vivo . 130 There are also therapies that have used immature cells that form part of the TME, such as MSCs. The replication potential and cytokine secretion capacity of these cells make them an excellent option for this type of treatment. 131 Neural stem cells can also be manipulated to produce and secrete apoptotic factors, and when these cells are incorporated into primary neural tumors, they cause a certain degree of regression. They can even be transfected with genes that encode for oncolytic enzymes capable of inducing regression of glioblastomas. 132

With respect to cell therapy using immune cells, several research groups have manipulated cells associated with tumors to make them effector cells and thus improve the efficacy and specificity of the antitumor treatment. PB leckocytes cultured in the presence of IL-2 to obtain activated lymphocytes, in combination with IL-2 administration, have been used in antitumor clinical protocols. Similarly, infiltrating lymphocytes from tumors with antitumor activity have been used and can be expanded ex vivo with IL-2. These lymphocyte populations have been used in immunomodulatory therapies in melanoma, and pancreatic and kidney tumors, producing a favorable response in treated patients. 133 NK cells and macrophages have also been used in immunotherapy, although with limited results. 134 , 135

One of the cell therapies with better projection today is the use of CAR-T cells. This strategy combines 2 forms of advanced therapy: cell therapy and gene therapy. It involves the extraction of T cells from the cancer patient, which are genetically modified in vitro to express cell surface receptors that will recognize antigens on the surface of tumor cells. The modified T cells are then reintroduced in the patient to aid in an exacerbated immune response that leads to eradication of the tumor cells ( Figure 4 ). Therapy with CAR-T cells has been used successfully in the treatment of some types of leukemia, lymphoma, and myeloma, producing complete responses in patients. 136

CAR-T cell therapy. (A) T lymphocytes obtained from cancer patients are genetically manipulated to produce CAR-T cells that recognize tumor cells in a very specific manner. (B) Interaction between CAR molecule and tumor antigen. CAR molecule is a receptor that results from the fusion between single-chain variable fragments (scFv) from a monoclonal antibody and one or more intracellular signaling domains from the T-cell receptor. CD3ζ, CD28 and 4-1BB correspond to signaling domains on the CAR molecule.

Undoubtedly, CAR-T cell therapy has been truly efficient in the treatment of various types of neoplasms. However, this therapeutic strategy can also have serious side effects, such as release of cytokines into the bloodstream, which can cause different symptoms, from high fever to multiorgan failure, and even neurotoxicity, leading to cerebral edema in many cases. 137 Adequate control of these side effects is an important medical challenge. Several research groups are trying to improve CAR-T cell therapy through various approaches, including production of CAR-T cells directed against a wider variety of tumor cell-specific antigens that are able to attack different types of tumors, and the identification of more efficient types of T lymphocytes. Furthermore, producing CAR-T cells from a single donor that may be used in the treatment of several patients would reduce the cost of this sort of personalized cell therapy. 136

Achieving wider use of cell therapy in oncologic diseases is an important challenge that requires solving various issues. 138 One is intratumor cell heterogeneity, including malignant subclones and the various components of the TME, which results in a wide profile of membrane protein expression that complicates finding an ideal tumor antigen that allows specific identification (and elimination) of malignant cells. Likewise, structural organization of the TME challenges the use of cell therapy, as administration of cell vehicles capable of recognizing malignant cells might not be able to infiltrate the tumor. This results from low expression of chemokines in tumors and the presence of a dense fibrotic matrix that compacts the inner tumor mass and avoids antitumor cells from infiltrating and finding malignant target cells.

Further Challenges in the 21st Century

Beyond the challenges regarding oncologic biomedical research, the 21 st century is facing important issues that must be solved as soon as possible if we truly wish to gain significant ground in our fight against cancer. Three of the most important have to do with prevention, early diagnosis, and access to oncologic medication and treatment.

Prevention and Early Diagnosis

Prevention is the most cost-effective strategy in the long term, both in low and high HDI nations. Data from countries like the USA indicate that between 40-50% of all types of cancer are preventable through potentially modifiable factors (primary prevention), such as use of tobacco and alcohol, diet, physical activity, exposure to ionizing radiation, as well as prevention of infection through access to vaccination, and by reducing exposure to environmental pollutants, such as pesticides, diesel exhaust particles, solvents, etc. 74 , 84 Screening, on the other hand, has shown great effectiveness as secondary prevention. Once population-based screening programs are implemented, there is generally an initial increase in incidence; however, in the long term, a significant reduction occurs not only in incidence rates, but also in mortality rates due to detection of early lesions and timely and adequate treatment.

A good example is colon cancer. There are several options for colon cancer screening, such as detection of fecal occult blood, fecal immunohistochemistry, flexible sigmoidoscopy, and colonoscopy, 139 , 140 which identify precursor lesions (polyp adenomas) and allow their removal. Such screening has allowed us to observe 3 patterns of incidence and mortality for colon cancer between the years 2000 and 2010: on one hand, an increase in incidence and mortality in countries with low to middle HDI, mainly countries in Asia, South America, and Eastern Europe; on the other hand, an increase in incidence and a fall in mortality in countries with very high HDI, such as Canada, the United Kingdom, Denmark, and Singapore; and finally a fall in incidence and mortality in countries like the USA, Japan, and France. The situation in South America and Asia seems to reflect limitations in medical infrastructure and a lack of access to early detection, 141 while the patterns observed in developed countries reveal the success, even if it may be partial, of that which can be achieved by well-structured prevention programs.

Another example of success, but also of strong contrast, is cervical cancer. The discovery of the human papilloma virus (HPV) as the causal agent of cervical cancer brought about the development of vaccines and tests to detect oncogenic genotypes, which modified screening recommendations and guidelines, and allowed several developed countries to include the HPV vaccine in their national vaccination programs. Nevertheless, the outlook is quite different in other areas of the world. Eighty percent of the deaths by cervical cancer reported in 2018 occurred in low-income nations. This reveals the urgency of guaranteeing access to primary and secondary prevention (vaccination and screening, respectively) in these countries, or else it will continue to be a serious public health problem in spite of its preventability.

Screening programs for other neoplasms, such as breast, prostate, lung, and thyroid cancer have shown outlooks that differ from those just described, because, among other reasons, these neoplasms are highly diverse both biologically and clinically. Another relevant issue is the overdiagnosis of these neoplasms, that is, the diagnosis of disease that would not cause symptoms or death in the patient. 142 It has been calculated that 25% of breast cancer (determined by mammogram), 50–60% of prostate cancer (determined by PSA), and 13–25% of lung cancer (determined by CT) are overdiagnosed. 142 Thus, it is necessary to improve the sensitivity and specificity of screening tests. In this respect, knowledge provided by the biology of cancer and “omic” sciences offers a great opportunity to improve screening and prevention strategies. All of the above shows that prevention and early diagnosis are the foundations in the fight against cancer, and it is essential to continue to implement broader screening programs and better detection methods.

Global Equity in Oncologic Treatment

Progress in cancer treatment has considerably increased the number of cancer survivors. Nevertheless, this tendency is evident only in countries with a very solid economy. Indeed, during the past 30 years, cancer mortality rates have increased 30% worldwide. 143 Global studies indicate that close to 70% of cancer deaths in the world occur in nations of low to middle income. But even in high-income countries, there are sectors of society that are more vulnerable and have less access to cancer treatments. 144 Cancer continues to be a disease of great social inequality.

In Europe, the differences in access to cancer treatment are highly marked. These treatments are more accessible in Western Europe than in its Eastern counterpart. 145 Furthermore, highly noticeable differences between high-income countries have been detected in the cost of cancer drugs. 146 It is interesting to note that in many of these cases, treatment is too costly and the clinical benefit only marginal. Thus, the importance of these problems being approached by competent national, regional, and global authorities, because if these new drugs and therapeutic programs are not accessible to the majority, progress in biomedical, clinical and epidemiological research will have a limited impact in our fight against cancer. We must not forget that health is a universal right, from which low HDI countries must not be excluded, nor vulnerable populations in nations with high HDI. The participation of a well-informed society will also be fundamental to achieve a global impact, as today we must fight not only against the disease, but also against movements and ideas (such as the anti-vaccine movement and the so-called miracle therapies) that can block the medical battle against cancer.

Final Comments

From the second half of the 20th century to the present day, progress in our knowledge about the origin and development of cancer has been extraordinary. We now understand cancer in detail in genomic, molecular, cellular, and physiological terms, and this knowledge has had a significant impact in the clinic. There is no doubt that a patient who is diagnosed today with a type of cancer has a better prospect than a patient diagnosed 20 or 50 years ago. However, we are still far from winning the war against cancer. The challenges are still numerous. For this reason, oncologic biomedical research must be a worldwide priority. Likewise, one of the fundamental challenges for the coming decades must be to reduce unequal access to health services in areas of low- to middle income, and in populations that are especially vulnerable, as well as continue improving prevention programs, including public health programs to reduce exposure to environmental chemicals and improve diet and physical activity in the general population. 74 , 84 Fostering research and incorporation of new technological resources, particularly in less privileged nations, will play a key role in our global fight against cancer.

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Hector Mayani https://orcid.org/0000-0002-2483-3782

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Guest Essay

Heavy Lies the Crown

By Tina Brown

Ms. Brown is the author of “The Diana Chronicles” and “The Palace Papers.”

I was in London last week when the febrile madness of Where Is Kate? was blowing up social media, and the Curious Mystery of the Doctored Mother’s Day Photograph consumed every news outlet and dinner table conversation.

After The Associated Press issued a kill notification on the botched photoshopped image of a suspiciously glossy Princess of Wales surrounded by her beaming progeny, there was a typical outburst of tabloid pomposity questioning whether Kensington Palace could ever be considered a trusted source of news.

Huh? When was the last time any tabloid considered the palace a trusted source of news? As the editor of Vanity Fair in 1985, I wrote a piece revealing that Prince Charles and Princess Diana were having awful marital fights. The palace roundly denied it, and the royal couple denied it in a television interview , confirming in my mind — correctly, as it turned out — that it was all true.

But this time, the volume and tenor of the gossip was off the charts. In all the raucous, salacious and often cruel rumormongering about Catherine, almost no one considered that behind the scenes something tragic was unfolding. When social media shrieked that there would be a very somber press announcement on Friday, royal-watchers assumed it would be from King Charles, who is battling an unspecified cancer .

But then the bombshell: Catherine announced in a video message that she, too, had cancer. After which there has rightly been a wave of cosmic shame about what this gracious public servant has been made to endure.

Catherine’s explanation of her cancer diagnosis was composed and moving, her face strained but brave. Filmed on a bench against a glimpse of spring daffodils, here was an ill woman trying to cope with a shocking diagnosis and painful medical treatment while shielding her young, worried children from the vultures of modern media.

I am told the turmoil behind the scenes has been intense, resulting in what has felt like a series of baffling press screw-ups. We hear often of Prince Harry’s hatred of the press . If possible, Prince William — while concealing it better — hates the press even more. His bloody-minded determination to stick to his grandmother Queen Elizabeth’s script of “never complain, never explain” is magical thinking in the era of the social media maelstrom, creating a vacuum filled by rumor and deranged conspiracy theories.

The almost simultaneous news of Charles’s cancer has put William and Catherine in frightening proximity to ascending the throne just when they had hoped for a span of years to parent their children out of the public eye. The prospect of it, I am told, is causing them intense anxiety.

Help from other family members is scant, aside from the redoubtable Princess Anne , Charles’s sister, and the good-egg Gaiety Girl Queen Camilla. The slimmed-down monarchy that Charles always promoted is suddenly looking very lean indeed. The combination of the Harry and Meghan clown show in Montecito, Calif.; the fusillades from Harry’s memoir, “ Spare ”; and the disgrace of Prince Andrew — who has little social contact with anyone except his horse — have put William and Catherine under unmanageable pressure.

Catherine is the most popular member of the royal family after William. The future of the monarchy hangs by a thread, and that thread is her.

It may not be a popular thought, but in many ways I blame the predicament and weakness of the monarchy today on Queen Elizabeth. It’s possible that future generations will see her as the Ruth Bader Ginsburg of the British monarchy. She stayed too long, and by doing so, left behind a legacy that may be the opposite of what she wanted.

The time for Elizabeth II to step down was not long after her Diamond Jubilee in 2012, the year I have come to think of as peak London, when Britain dazzlingly hosted the Olympics. Elizabeth II had embarked on a triumphantly healing visit for the first time to the Republic of Ireland in 2011 , Charles proved he was a settled married man at last to Camilla, Harry was a national hero after two military tours of Afghanistan, and William and Kate Middleton had recently tied the knot at Westminster Abbey in a blaze of national good will.

It would have been such a gift to her heirs if at that glorious moment Elizabeth II had stepped aside, as Margrethe II, the queen of Denmark, did in January 2024. After 52 years on the throne, she announced her abdication in her New Year’s address with the elegant explanation that “the time takes its toll.”

Instead, Elizabeth II stayed on some 10 years — to the end. Apparently to honor her oath to serve “my whole life, whether it be long or short,” but actually because she loved her job. She had seen how bored and marginalized the Queen Mother felt when, widowed young by George VI and deprived of power dinners with heads of state or the inside scoop from her husband’s tête-à-têtes with the prime minister, she was relegated to boring rounds of cutting ribbons in those huge feathery hats . No, Elizabeth II loved the world of politics and power as much as she did breeding horses and tramping the heather of her Balmoral estate.

But her 70-year reign has left a pileup of heirs infantilized by too little to do and trapped by a dusty structure that should have been reformed decades ago.

Charles, full of prescient ideas, inventive concepts of philanthropy and imaginative plans of how to modernize the monarchy, saw his hopes and dreams curdle as he waited and waited to put them into action. The beleaguered flexitarian was allowed to marry the woman he loved only when he was 56 years old. Even with the best prognosis for his cancer, he has been left with a rueful rump of a reign. His sad-sack motto was always “just my luck,” but that has never seemed more true than now.

And William, instead of taking over the Duchy of Cornwall estates in his early 30s and creating a space for the popular Harry to develop a strong portfolio of his own, ended up in a rivalrous relationship with his younger brother that exploded irretrievably when Meghan Markle entered the scene. A less hidebound palace might have come up with a more creative way to solve the Sussex imbroglio.

The fascination of the crown will always be the tension between a venerable institution and the human beings who are trapped inside it. Isn’t it just too cruel to expect modern mortals to live and love and parent in such a blisteringly unforgiving media gaze?

Catherine is battling more — much more — than cancer. A tidal wave of premature responsibility is crashing in her and William’s direction. Frozen, unready and with Catherine now seriously unwell, the Prince and Princess of Wales await the awesome burden of the crown.

Tina Brown is the author of “The Diana Chronicles” and “The Palace Papers.”

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A new type of bacteria was found in 50% of colon cancers. Many were aggressive cases.

A type of bacteria that causes dental plaque may be behind a treatment-resistant form of colorectal cancer, a study published Wednesday in the journal Nature found.

The particular bacterium, which appears to shield tumor cells from cancer-fighting drugs, was found in 50% of the tumors tested in the study. The discovery, experts say, could pave the way for new treatments and possibly new methods of screening.

Colon cancer is the second-leading cause of cancer deaths in the United States and is expected to kill more than 53,000 people in the nation in 2024, according to the American Cancer Society . 

Rates are rising sharply among younger people: The percentage of people younger than 55 diagnosed with colon cancer almost doubled between 1995 and 2019, leaping from 11% to 20% of cases. What’s more, these cases are often diagnosed at later, more aggressive stages .

Experts are still struggling to explain the shift.

“Colorectal cancer is very treatable when caught early, but the cases in younger people are increasing and we don’t know why,” said Dr. Flavio Rocha, a surgical oncologist and physician in chief at the Oregon Health & Science University’s Knight Cancer Institute, who was not involved in the study. 

The new research doesn’t answer that question; it’s far too early to implicate this bacteria in the rise in cases in younger people . What’s more, most of the patients in the study were over the age of 50.

But the findings raise “the question as to whether there are elevated levels of this bacterium in young onset colorectal cancer which is on the rise globally for unknown reasons,” said co-lead study author Susan Bullman, an assistant professor of human biology at the Fred Hutchinson Cancer Center in Seattle.

Bacteria with a secret

Scientists have suspected a link between the bacteria, called Fusobacterium nucleatum, and colorectal cancer growth for almost a decade. The bacteria is usually only found in the mouth, far from the colon. 

In the mouth, it’s one of the most common types of disease-causing bacteria , linked to gum disease and plaque buildup. But it was unclear how it could withstand the journey through the gut and eventually invade tumor cells in places in the body where these types of bacteria usually don’t survive.

In the study, Bullman and her colleagues looked at the bacterial makeup of almost 200 colorectal tumors, as well as stool samples from more than 1,200 people, half of whom did not have cancer. 

What they learned was that the bacteria was a bit more complicated than once thought. Namely, it has two distinct subspecies, one of which appears to shield colorectal tumors from cancer-fighting drugs. 

“It acts like a cloak,” Bullman said. 

Normally, immune cells called T-cells recognize and attack tumor cells. But this bacteria recruits another type of immune cell into the cancer cells, one that lets them escape the T-cells.

The stealthy subspecies was present in 50% of the colorectal tumors collected in the study. The corresponding stool samples also had elevated amounts of the subspecies, compared to their healthy counterparts. 

“Patients who have high levels of this bacteria in their colorectal tumors have a far worse prognosis ,” Bullman said. “They don’t respond as well to chemotherapy and they have an increased risk of recurrence.” 

The subspecies may also cause cancer to form in the first place. 

When Bullman and her team transplanted the subspecies to mice, they appeared to cause precancerous polyps to form, one of the first warning signs of colorectal cancer, though she added that this causation hasn’t yet been proven in humans.

The researchers also found clues that may answer the question as to how Fusobacterium nucleatum can get to the colon in the first place: The bacterium appears to be able to survive the journey through the stomach, withstanding what scientists previously thought would be a toxic dose of stomach acid. 

New targets for treatment

The discovery of the subspecies has huge consequences for targeted therapies that are already underway, said Dr. Michael White, an assistant professor of colorectal surgery at The University of Texas MD Anderson Cancer Center in Houston.

“There is evidence that if you clear these bacteria, there is more response during treatment,” said White, who was not involved with the new research. Clinical trials are slated to soon test whether treating a patient with antibiotics prior to chemotherapy will induce a better response, he said.

Knowing more about which bacterial subspecies, including Fusobacterium nucleatum, are dangerous will allow for a more targeted approach, he said. 

That could potentially include prevention.

It’s possible that scientists could identify the subspecies while it’s still in the mouth and give a person antibiotics at that point, wiping it out before it could  travel  to the colon, Bullman said. Even if antibiotics can’t successfully eliminate the bacteria from the mouth, its presence there could serve as an indication that someone is at higher risk for aggressive colon cancer, she added. 

Rocha agreed. In the future, part of colorectal cancer screening could be as simple as a mouth swab, he said. 

Understanding the newly identified subspecies could also lead to the development of new antibiotics that would specifically target this bacterial subtype, rather than wiping out both forms of the bacteria or all of the bacteria in the mouth.

There’s also the possibility of harnessing the bacteria to do the cancer-fighting work. 

The subtype has already proven that it can enter cancer cells quite easily, so it might be possible to genetically modify the bacteria to carry cancer-fighting drugs directly into the tumors, Bullman said.

Researchers are just beginning to scratch the surface of the ways a person’s microbiome plays a role in the individual’s cancer risk, Rocha said, but it’s one of the most important concepts being explored in cancer research today.

Kaitlin Sullivan is a contributor for NBCNews.com who has worked with NBC News Investigations. She reports on health, science and the environment and is a graduate of the Craig Newmark Graduate School of Journalism at City University of New York.

I Hope You All Feel Terrible Now

How the internet—and Stephen Colbert—hounded Kate Middleton into revealing her diagnosis

Updated at 4:04 p.m ET on March 22, 2024

For many years, the most-complained-about cover of the British satirical magazine Private Eye was the one it published in the week after the death of Diana, Princess of Wales, in 1997. At the time, many people in Britain were loudly revolted by the tabloid newspapers that had hounded Diana after her divorce from Charles, and by the paparazzi whose quest for profitable pictures of the princess ended in an underpass in Paris.

Under the headline “Media to Blame,” the Eye cover carried a photograph of a crowd outside Buckingham Palace, with three speech bubbles. The first was: “The papers are a disgrace.” The next two said: “Yeah, I couldn’t get one anywhere” and “Borrow mine, it’s got a picture of the car.” People were furious. Sacks of angry, defensive mail arrived for days afterward, and several outlets withdrew the magazine from sale. (I am an Eye contributor, and these events have passed into office legend.) But with the benefit of hindsight, the implication was accurate: Intruding on the private lives of the royals is close to a British tradition. We Britons might have the occasional fit of remorse, but that doesn’t stop us. And now, because of the internet, everyone else can join in too.

Read: Just asking questions about Kate Middleton

That cover instantly sprang to mind when, earlier today, the current Princess of Wales announced that she has cancer. In a video recorded on Wednesday in Windsor, the former Kate Middleton outlined her diagnosis in order to put an end to weeks of speculation, largely incubated online but amplified and echoed by mainstream media outlets, about the state of her health and marriage.

Kate has effectively been bullied into this statement, because the alternative—a wildfire of gossip and conspiracy theories—was worse. So please, let’s not immediately switch into maudlin recriminations about how this happened. It happened because people felt they had the right to know Kate’s private medical information. The culprits may include three staff members at the London hospital that treated her, who have been accused of accessing her medical records, perhaps driven by the same curiosity that has lit up my WhatsApp inbox for weeks. Everyone hates the tabloid papers, until they become them.

In her statement, Kate said that after her abdominal surgery earlier in the year, which the press was told at the time was “planned”—a word designed to minimize its seriousness—later tests revealed an unspecified cancer. She is now undergoing “preventative chemotherapy,” but has not revealed the progression of the disease, or her exact prognosis. “I am well,” she said, promising that she is getting stronger every day. “I hope you will understand that as a family, we now need some time, space and privacy while I complete my treatment.”

This news will surely make many people feel bad. The massive online guessing game about the reasons for Kate’s invisibility seems far less fun now. Stephen Colbert’s “spilling the tea” monologue , which declared open season on the princess’s marriage, should probably be quietly interred somewhere. The sad simplicity of today’s statement, filmed on a bench with Kate in casual jeans and a striped sweater, certainly gave me pause. She mentioned the difficulty of having to “process” the news, as well as explaining her condition to her three young children in terms they could understand. The reference to the importance of “having William by my side” was pointed, given how much of the speculation has gleefully dwelt on the possibility that she was leaving him or vice versa.

Read: The eternal scrutiny of Kate Middleton

However, the statement also reveals that the online commentators who suggested that the royal household was keeping something from the public weren’t entirely wrong. Kate’s condition was described as noncancerous when her break from public life was announced in late January . The updated diagnosis appears to have been delivered in February, around the time her husband, Prince William, abruptly pulled out of speaking at a memorial service for the former king of Greece. Today’s statement represents a failure of Kensington Palace to control the narrative: first, by publishing a photograph of Kate and her children that was so obviously edited that photo agencies retracted it, and second, by giving its implicit permission for the publication of a grainy video of the couple shopping in Windsor over the weekend. Neither of those decisions quenched the inferno raging online—in fact, they fed it.

Some will say that Kate has finally done what she should have done much earlier: directly address the rumors in an official video, rather than drip-feed images that raised more questions than they answered. King Charles III has taken a different approach to his own (also unspecified) cancer, allowing footage to be filmed of him working from home. But then again, Kate has cancer at 42, is having chemo, and has three young children. Do you really have it in you to grade her media strategy and find it wanting?

Ironically, Britain’s tabloid papers have shown remarkable restraint; as I wrote earlier this month , they declined to publish the first paparazzi pictures of Kate taken after her withdrawal from public life. They have weighted their decisions toward respect and dignity—more so than the Meghan stans, royal tea-spillers, and KateGate theorists, who have generated such an unstoppable wave of interest in this story that its final destination was a woman with cancer being forced to reveal her diagnosis. If you ever wanted proof that the “mainstream media” are less powerful than ever before, this video of Kate Middleton sitting on a bench is it.