Advancing Cancer Prevention: A Conversation with NCI’s Dr. Philip Castle

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July 20, 2021, by NCI Staff

Cancer Prevention word cloud

Philip Castle, Ph.D., M.P.H., joined NCI in July 2020 as director of the Division of Cancer Prevention (DCP). Dr. Castle previously worked at NCI in the Division of Cancer Epidemiology and Genetics (2002–2010), where he led numerous research projects, including studies of HPV and its connection to cervical and anal cancers. To mark his first year as DCP director, Dr. Castle discusses DCP’s priority areas and his vision for making more rapid progress in cancer prevention.

What do you see as the most promising possibilities for, and barriers to, real progress in cancer prevention over the next decade?

There are a variety of areas of promise. One area that we’re working very hard to develop is precision cancer prevention. What I mean by that is using what we know about a person—their genetics, risk factors, lifestyle—to tailor our prevention strategies. And as an anchor to that, we’re using molecular sciences to flesh out the best approaches for advancing this work.

At the same time, we want to democratize cancer prevention, developing new strategies that make proven prevention measures more broadly accessible, particularly for underserved populations. For instance, efforts to expand the use of self-sampling with HPV DNA testing for cervical cancer screening.

As for barriers to progress, I see two major issues. One that has been called the “prevention paradox”: If we’re successful with prevention, there’s nothing to observe because we’ve avoided a bad outcome—cancer. It’s what I call an “event bias,” where we tend to notice the events that occur rather than the absence of events. That’s a real hurdle, particularly for getting people to recognize the importance of prevention and support for prevention research. There is no prevention equivalent to a cancer champion.

A second barrier is the benefits-to-harms ratio of any prevention-focused interventions. When you’re talking about cancer prevention, you’re primarily dealing with generally healthy people. So the tolerance for any side effects from a prevention intervention is very low. Many people won’t get cancer in their lifetime, and you don’t want to harm anybody who was never going to get cancer. That’s the struggle we’re up against.

Prevention is a broad topic. Have you identified priority areas for the division?

Yes, there are three research arcs we’re focused on.

One is developing preventive agents. That involves identifying “druggable” targets for preventive drugs and developing the drugs themselves. That work is anchored in molecular sciences, understanding cancer-promoting signaling pathways in cells and how to interrupt them, and using that information to develop new pharmacologic agents or repurpose existing drugs for use in cancer prevention.

The second research arc is discovering biomarkers that can identify who is at increased risk of cancer. Eventually, those two areas will come together: We will be able to use a biomarker that can identify who’s at risk, and then provide a preventive agent to mitigate that risk, based on an individual’s underlying biology.

It’s about understanding who is at high risk and developing and implementing risk-informed interventions while identifying those at lower risk and backing off. It’s not one-size-fits-all prevention.

The third relates to improving symptom management in those with cancer who are undergoing treatment, which is also a part of DCP’s research portfolio. And, just like we want to do for prevention and treatment, we also want to make symptom management more precise. So we need to better understand the biology behind a person’s symptoms due to cancer and their responses to treatments.

Once we understand the biology and genetics of cancer-related and treatment-related symptoms—that is, symptom science—we can better tailor the use of current medications to prevent and/or alleviate symptoms and develop new, more effective medications in the future.

This has an important impact on survivorship: The longer we keep people with cancer healthy, the more likely they are going to be able to get the next-in-line therapy and even therapies that have not been invented today but will be tomorrow.

A big part of prevention is early detection. There’s been recent progress in the development of multicancer early detection tests. What are your thoughts about these tests?

There is clearly a tremendous amount of promise and excitement with these multicancer early detection tests, which are single tests that can potentially identify the presence of multiple cancers. And that includes cancer types for which there are currently no screening tests.

However, if we’re looking at the available evidence objectively, to date all these tests have shown is that they can detect cancer. The big question is: Can we detect the cancer at an early enough stage that we reduce the risk of death from that cancer? That’s the litmus test for any cancer screening test.

Along those lines, I fully support [NCI Director] Dr. Sharpless’s call for NCI to conduct a large clinical trial to try to answer that question.

Diet and exercise are areas of intense interest in cancer prevention. Where do you think these two areas fit into the overall prevention picture?

The thought is definitely out there that if you eat this specific thing or avoid this other thing, you’ll prevent cancer. Unfortunately, no specific foods or activities are proven to prevent cancer, except perhaps avoiding cooked red meat, and there are numerous factors that make research to identify such factors difficult to do.

Still, we know that obesity increases the risk for about 13 cancers. And we know that a healthy lifestyle, including weight management, will likely reduce your cancer risk. Of course, not everyone has equal access to healthy foods and things that promote healthy behaviors and much of that is influenced by policy matters.

But from a research perspective, one of the things we can do is find innovative ways to educate people about how to achieve a healthier lifestyle and interrupt the cycle of obesity, not just for cancer health but for their overall health.

Immunotherapy is now being studied as a potential way to help prevent cancer. Where does this research stand?

Immunotherapy has been a great advance for cancer treatment. So this “immunoprevention” research is essentially looking at whether we can harness the immune system as a form of cancer surveillance, to detect and snuff out cells with the earliest changes that will lead to cancer.

In DCP, we’re starting a new initiative to promote the discovery of preventive therapies, and that will include some immunoprevention drugs. In particular, we’re expanding activities around developing preventive agents for those at high risk for cancer, such as those with a genetic predisposition like Lynch syndrome. The idea is to start this work with a focus on the highest-risk groups, make progress for them, and then apply what we learned and work towards immunoprevention in people who are at average risk.

Some drugs have been approved for cancer prevention or risk reduction, such as tamoxifen for breast cancer, but few people have chosen to use them. Are you concerned that could happen with any new prevention drugs?

It’s an important issue. Let’s take aspirin, for example. If you’re at high risk of colorectal cancer and/or cardiovascular disease, it may make complete sense to take low-dose aspirin. However, if you walk down the street and ask somebody if they knew aspirin was a preventive agent for colorectal cancer, as hard as it might be to believe, some might say, “What is colorectal cancer?” These are real issues. And they show that a big part of our challenge is education and communication.

We know that one of the barriers of using tamoxifen as a preventive agent is its toxicity—that benefits-to-harms ratio I mentioned earlier—especially if used over long periods of time. But just as we are looking at innovative ways to deliver screening tests, there are innovative ways to deliver preventive agents so more of the drug gets to the tissue we are trying to protect and less to the other places in the body where the toxicity may occur.

In the case of tamoxifen, for example, we are funding an early-phase clinical trial on topical tamoxifen delivered to the breasts of women at high risk of breast cancer and the results to date are very promising.

Do physicians have a major role there, in educating and communicating about cancer risk and prevention?

Absolutely. We know most people feel that their doctors are the most trusted sources of medical information. But we also know that many physicians are already overwhelmed with what’s on their shoulders. They can’t spend an hour in consultation with every patient. In addition, they may not be fully up to date on the latest science. We need to educate the educator.

So we’re going to have to rely on other health experts—nurse practitioners, community health workers—to convey information about the importance of activities that promote good health, including reducing cancer risk. That means that we need to educate them as well.

What role do you see technology playing in advancing progress in prevention?

Of course it plays a very important role. As a consequence, [in DCP], we’re going to be looking for a chief technical officer to guide us in the use of new technologies for prevention.

One area where technology can have an important role is making screening tests better and faster, with point-of-care testing that can provide the results in the same day as the patent’s clinic visit. That can help reduce the number of people we lose to follow up, which is still too many.

In fact, we’re working with NCI’s SBIR program to promote the development of rapid HPV tests and at-home [hepatitis C virus (HCV)] testing. In the latter case, for example, chronic HCV infection can lead to liver cancer, but most HCV carriers don’t know that they’re carriers.

We now have very good antiviral treatments for HCV, but you can’t do anything about an infection you don’t know about. So a rapid at-home test could be an important prevention tool. As we have learned again and again, now from the COVID-19 pandemic, access is a key determinant to who participates in preventive services.

What do you see as the most important messages when it comes to cancer prevention?

I think it’s coming back to first principles. There’s that old saying: “An ounce of prevention is worth a pound of cure.” Imagine what a pound of prevention would be worth! However, that won’t happen without a philosophical shift in what we emphasize as the first line against cancer. Nobody, and I mean nobody, wants to get cancer.

And it’s important to say that we’re not going to prevent all cancers. That’s not going to be possible. But we need to take advantage of [the preventive measures] we have now. In addition, we need to press forward in a very concerted way so that we better understand the cancer process, and learn to identify who is at most risk and neutralize that risk before they develop cancer through innovative cancer prevention research.

I believe that we are entering the golden age of cancer prevention and I will do everything I can to help usher it in.

“Advancing Cancer Prevention: A Conversation with NCI’s Dr. Philip Castle was originally published by the National Cancer Institute.”

Diversity Lacking in Pancreatic Cancer Trials

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From Let’s Win! Pancreatic Cancer
August 6, 2021

Pancreatic cancer trials are no exception. A recent study selected for presentation at the annual Digestive Disease Week 2021 conference clearly shows the magnitude of the problem.

Researchers analyzed data from 8,429 participants in 207 clinical trials in the U.S. for treatments for pancreatic ductal adenocarcinoma on ClinicalTrials.gov, the national registry of clinical trial data. Gender was reported in 99 percent of the trials, while race and ethnicity were reported in 49.3 percent and 34.7 percent of trials respectively. In all, 54.8 percent of trial participants were male, and 45.2 percent were female.

According to the data, minorities were substantially underrepresented:

  • Black patients comprised 8.2 percent of trial participants vs. 12.4 percent of cases
  • Hispanic patients represented 6 percent of trial participants vs 8.5 percent of cases
  • Asian or Pacific Islander patients represented 2.4 percent of trial participants vs 3.3 percent of patients
  • American Indians and Alaska Native patients represented 0.3 percent of trial participants compared to 0.4 percent of cases

On the flip side, White patients were overrepresented, making up 84.7 percent of the total trial participants, while they account for 82.3 percent of the total U.S. pancreatic cancer incident cases.

“We knew there was an issue and we knew there were going to be disparities, but when we looked at the numbers we were a little shocked. Anyone who isn’t White is underrepresented in these trials,” says lead investigator Kelly Herremans, M.D., a general surgery resident and surgical oncology research fellow at the University of Florida, Gainesville, who presented the abstract “Trials and tribulations: Diversity and inclusion in pancreatic ductal adenocarcinoma clinical trials.”

The hypothesis for the study stemmed from what was being seen in the clinic. “As a surgical oncologist who concentrates his academic and clinical practice on pancreatic cancer, I was seeing mostly White people coming in the door while pancreatic cancer disproportionately affects Black Americans,” explains surgical oncologist Jose Trevino, M.D., Chair of the Division of Surgical Oncology at the VCU School of Medicine and Surgeon-in-Chief at VCU Massey Cancer Center, Virginia Commonwealth University, Richmond.

Trevino admits this contradictory scenario spurred a lot of questions. “I started asking myself if this was a result of socioeconomics, lack of transportation, or that minorities don’t always trust the healthcare system,” he notes. Trevino’s research focuses on pancreatic cancer biology, tumor microenvironment, cancer cachexia, and novel therapeutics and how they relate to pancreatic cancer health equity. “When you see the numbers, the disparity in recruitment is just so stark.”

Asking the Tough Questions

Lack of diversity in clinical trials is often attributed to reluctance to participate due to historic wrongs, such as the infamous 1932 USPHS Syphilis Study at Tuskegee that left Black men untreated for many years to study the long-term impact of syphilis. But research has shown that Black patients are just as willing as White patients to be part of a clinical trial, Herremans says. Plus, Black patients get pancreatic cancer more often, are diagnosed at younger ages, and die sooner, she adds.

Which, of course, begs the question: Why then is there such underrepresentation?

The research team is currently in the process of trying to answer that question. “It’s clearly multifactorial,” Herremans explains. “But one reason may be due to the fact there are so few Black or Hispanic oncologists, for example, which can influence referral patterns.”

Other troubling reasons for the lack of minority enrollment may be due to systemic racism, provider biases that interfere with recruitment as well as study inclusion criteria. Those biases can create impediments to enrollment, such as turning away patients with obesity and diabetes, which are more prevalent in minority populations.

“As doctors who deal with cancer patients every day, we need to start looking at ourselves,” says Trevino. “I’m a surgeon. Dr. Herremans is a surgeon. If something goes wrong in the operating room the first person we look at is ourselves and ask what did we do wrong? We don’t blame the tools or the system because we can’t exclude the possibility that we made a mistake.

“So when you think of it that way, we need to ask ourselves why is the accrual so poor?”

Because of higher rates of diabetes and heart disease among minority patients, they often don’t meet eligibility requirements for trials, Trevino explains. “Many trials are designed for the healthiest of pancreatic cancer patients. That’s going to immediately exclude many minority participants and that just doesn’t make sense.”

Both Trevino and Herremans admit some of the questions they will ask as their research progresses may be uncomfortable. “We’re going to be asking tough questions, and venture into areas that people have stayed away from, and then hopefully find ways to better meet the needs of all cancer patients,” Trevino says. “That’s the way that change occurs.”

Why Diversity Matters

Clinical trials are the foundation of approval for any new cancer chemotherapeutic agent. Without demographic diversity among those who participate in trials, researchers won’t have a clear understanding of how the drug may work in different populations.

Numerous variables, including age, sex, and ethnicity, among others, can influence how an individual may react to a drug. For example, a 2014 study published in the journal Clinical Pharmacology & Therapeutics found marked differences as to how different ethnicities reacted to about 20 percent of drugs approved from 2008 to 2013.

That’s because tumor biology plays a role. “What we do know is that patients with African ancestry have different rates of both somatic and germline mutations when compared to other subgroups,” Herremans explains. “They are going to respond differently to therapies.

“I’m completing a precision medicine fellowship right now, and the bulk of the subject matter is how patient biology impacts therapeutics. Everyone is unique. Patients of different ancestries may metabolize things differently based on enzymes. So there has to be adequate representation of different races and ethnicities in clinical trials because without that we just don’t know how that particular drug is going to act in all patients.”

Both researchers are hopeful there will be change sooner rather than later. “There are regulations that are supposed to help with this problem, and everyone is talking about the issue. I think it’s just time that we all just need to work together, move forward, and make changes that need to be made,” Herremans notes.

Precision medicine will also be a game-changer. “I am Mexican, but that means I’m probably a mix of Portuguese, Spanish, and Indigenous American ancestry,” says Trevino. “We’re all a mix of something. Ideally, we will get to the day when therapies are based on individual patient genomics. We’re not quite there yet, but when we are it will be a beautiful day.”

 

Understanding Cancer Research Study Design and How to Evaluate Results

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Approved by the Cancer.Net Editorial Board, 04/2018

Doctors and scientists conduct research studies to find better ways to prevent and treat cancer. Depending on the questions they want to answer, researchers can design these studies in different ways. No study design is perfect. Each has strengths and drawbacks. It is important to understand a study’s design. By doing this, you can understand the results to know if they apply to your situation.

In cancer research, there are 2 main types of research studies:

  • Experimental studies. This type of study provides an intervention, such as a new treatment. The intervention is given to a group of people. Then, researchers compare their results to those of another group that does not receive the intervention. This other group is known as the control group. The researchers choose who does and does not receive the intervention either randomly or through a selection process. Experimental studies help researchers learn more about how cancer starts or spreads. These studies can also test new imaging techniques and explore quality of life issues.
  • Observational studies. This type of study involves observing groups of people in a natural setting and looking at a specific result. A result may include whether 1 group of people has more cancer diagnoses than another group. In these studies, the researchers cannot control the intervention, such as a person’s weight or whether they took vitamin supplements. These studies are often described as epidemiologic. Epidemiology involves studying how different risks cause or spread a disease in a community.

Types of experimental studies

Experimental studies are more reliable than observational studies. This is because the volunteers are placed in the intervention or control group by chance. This reduces the likelihood that the assumptions or preferences of the researchers or volunteers will change the study results. Such assumptions or preferences are called bias.

This type of study also helps researchers to better find and control other factors, such as age, sex, and weight. These factors can affect the results of the study.

Researchers may also consider certain factors when choosing people to enroll in an experimental study. They could be based on type of cancer, stage of the disease, or whether the cancer has spread.

One of the most common types of experimental studies is the clinical trial. This is a research study that tests a medical intervention in people. Clinical trials test:

  • The effectiveness or safety of a new drug or combination of drugs
  • A new approach to radiation therapy or surgery
  • A new treatment or way to prevent cancer
  • Ways to lower the risk of cancer coming back

Doctors and researchers conduct clinical research in segments called phases. Each phase of a clinical trial provides different answers about the new treatment. For instance, it can show the dose, safety, and efficacy of the treatment. The efficacy is how well the treatment works. There are 4 phases of clinical trials.

In a clinical trial, volunteers are usually selected by chance to either be in the treatment or control group. Researchers can prevent bias in a clinical trial by keeping volunteers and/or themselves from knowing how the volunteers are grouped. This is a process known as “blinding.”

Types of experimental studies include:

  • Double-blind randomized trial. Most scientists believe this type of clinical trial will produce the best evidence in a study. Neither the volunteers nor the researchers know who belongs to a treatment or control group until the study ends.
  • Single-blind randomized trial. In this type of trial, the volunteers do not know whether they belong to a treatment or control group. But the researchers know.
  • Open/unblinded trial. Both volunteers and researchers know who belongs to each test group in this type of study. This occurs when it is not possible to use blinding. For instance, the study could compare a surgical treatment to a drug.

Types of observational studies

In observational studies, researchers have less control over the study volunteers. This means that certain factors could affect the results. These studies, however, are useful in providing initial evidence that can help guide future research.

Types of observational studies include:

  • Case-control studies. These types of studies compare 2 groups of people. For instance, they could compare those who have cancer (the case) and those who do not (the control). Researchers may look for lifestyle or genetic differences between the 2 groups. By doing this, they hope to find out why 1 group has a disease and the other group does not. These studies are conducted retrospectively. That is, they are researching what has already happened.
  • Cohort studies. These studies are prospective, which means that researchers study the event as it occurs. They monitor a group of people for a long time and track something. For example, they could track any new cancer diagnoses. This type of study can assess whether certain nutrients or actions can prevent cancer. This approach can also find cancer risk factors. For instance, cohort studies have looked at whether postmenopausal hormone replacement therapy increases the risk of breast cancer.
  • Case reports and case series. These studies are detailed descriptions of a patient’s medical history. The individual patient descriptions are called case reports. If many patients receive a similar treatment, the case reports may be combined into a case series. The results of case series studies are descriptions of patients’ histories within a specific group. As such, they should not be used to determine treatment options.
  • Cross-sectional studies. These studies examine how diseases interact with other factors within a specific group at a point in time. But because these studies only measure interactions at a single point in time, they cannot prove that something causes cancer.

Types of review articles

A large number of cancer research studies are published every year. Given this, it is challenging for doctors, as well as interested patients and caregivers, to keep up with the latest advances. Research studies published in journals are constantly shaping and reshaping the scientific understanding of that subject. No single study provides the final word on a topic, type of cancer, or treatment. As a result, review articles, which evaluate and summarize the findings of all published research on a certain topic, are extremely helpful.

Types of review articles include:

  • Systematic reviews. These articles summarize the best available research on a specific topic. Researchers use an organized method to locate, gather, and evaluate a number of research studies on a particular topic. By combining the findings of a number of studies, researchers are able to draw more reliable conclusions.
  • Meta-analyses. These studies combine data from several research studies on the same topic. By combining these data, a meta-analysis can find trends that are hard to see in smaller studies. But if the single studies were poorly designed, the results of the meta-analysis may not be useful.

Evaluating research studies

Here are some tips for finding out the quality of a research study:

  • Find out if the journal uses a peer-review process. Results from a study are more reliable if they are peer-reviewed. This means that researchers who are not a part of the study have looked over and approved the design and methods.
  • Look at the length of the study and the number of people involved. A study is more useful and credible if the same results occur in many people across a long time. Studies of rare types of cancer or cancers with a poor chance of getting better are an exception to this rule. This is because there are a small number of patients to study. Also, when looking at the length of the study, it may be suitable for some clinical trials to be shorter. For instance, cancer prevention trials are often much longer than treatment clinical trials. This is because it usually takes longer to figure out if a prevention strategy is working compared to a treatment.
  • Consider the phase of the study when learning about new treatments. Phase I and II clinical trials usually tell you more about the safety of a treatment and less about how well it works. These studies tend to have a smaller number of patients compared to phase III clinical trials.  Phase III clinical trials compare a new treatment with the standard of care. “Standard of care” means the best treatments known. Doctors consider phase III clinical trials to be the most reliable.
  • Find out if the study supports or contradicts current research. New results are exciting, but other researchers must validate the results before the medical field accepts them as fact. Review articles like systematic reviews are of special interest. They review and draw conclusions across all of the published research on a specific topic.
  • Watch out for conclusions that overstate or oversimplify the results. Each study is a small piece of the research puzzle. Medical practice rarely changes because of the results of a single study.

Questions to ask your health care team

Always talk to your health care team about what you find in an abstract or study. If you have reviewed a study that suggests a different approach to cancer treatment, do not stop or change your treatment. First talk with your health care team about how the study relates to your treatment plan.

Consider asking your health care team the following questions:

  • I recently heard about a study that used a new treatment. Is this treatment related to my type and stage of cancer?
  • What type of journals should I read to learn more about my type of cancer?
  • Should I consider being a part of a clinical trial?
  • What clinical trials are open to me?
  • Where can I learn more about clinical trials?

Cancer Research Starts Here

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Much of the recent improvement in 5-year survival rates for all cancers combined is the result of discoveries across the past five decades that have shaped our understanding of what cancer is, its biological and social risk factors, and how it grows and spreads. Thanks to the individuals who perform this research, more lives have been saved and great strides were made in preventing, diagnosing, and treating this collection of diseases.

Earlier Breakthroughs That Paved the Way for Progress

From left, Drs. Joseph Fraumeni, Jr., Harold Varmus, Joan Steitz, Jim Allison, and Steven Rosenberg.

Credit: National Cancer Institute, Copyright held by, and used with permission of, The Board of Regents of the University of Texas System through The University of Texas MD Anderson Cancer Center

Dr. Joseph Fraumeni, Jr.

Developed the first computer-generated maps linking cancer and the environment

Back in the 1970s when computers still weren’t in most homes, Dr. Joseph Fraumeni, Jr., created the first computer-generated maps that showed groupings of cancer deaths in US counties. These maps opened our eyes to the link between cancer and the environment and helped solidify Dr. Fraumeni’s position as a pivotal figure in public health. Even before that, together with NCI colleague Dr. Frederick Li, he discovered Li-Fraumeni syndrome—a rare, inherited disorder that greatly increases risk for several types of cancer, particularly in children and young adults. And as founding director of NCI’s Division of Cancer Epidemiology and Genetics, he was an early advocate for disparities research at the institute. Across a trailblazing career, Dr. Fraumeni has attributed his success to a series of mentors and colleagues, and to his wife, whom he credits with encouraging him and keeping him focused over more than 40 years of marriage.

Dr. Harold Varmus

Discovered that cancer comes from mutations in normal genes

More interested in talking about plays and poetry in college, Dr. Harold Varmus graduated with two literature degrees before pursuing medicine. Feeling drawn to the study of the scientific basis of disease, he came to NIH in 1968 and set his sights on a career in basic research. On a backpacking trip to California the next year, Dr. Varmus met Dr. J. Michael Bishop, the man he’d go on to share a Nobel Prize with in 1989 for their novel theory on the origin of cancer. They found that cancer comes from mutations in certain normal genes in a range of species and that these mutations are triggered by random errors in normal cell division or by other external causes. Along with this major discovery, Dr. Varmus has spent decades advancing scientific knowledge and has held several key positions, including as director of NIH, and later, NCI.

Dr. Joan Steitz

Pioneered the study of RNA biology and RNA’s role in cancer development

With no female professors or women running labs around her in the 1960s, Dr. Joan Steitz initially never thought to aspire to such a role herself. Even her first choice for doctoral advisor turned her away, stating that, as a woman, she would just get married and have a family. Despite this, she went on to head her own lab at Yale University in 1970, just one year after the school first accepted female undergraduates, and became a pioneer in the field of RNA biology. Her lab has made fundamental discoveries about the roles of non-coding RNAs in many areas of biology, including cancer. She’s obtained many prestigious awards, including the National Medal of Science as well as a 2018 Lasker Award for her research and mentorship and support of women in science. As a mentor, Dr. Steitz has tirelessly campaigned for inclusive practices within the scientific community and research workforce, speaking out about biases that harmfully affect women and minorities in science.

Dr. Jim Allison

Created a therapy using one’s own T cells to fight cancer

Among the many talented scientists that make up The CheckPoints band, harmonica player Dr. Jim Allison stands out—and it’s not just because he has played with Willie Nelson or because he is the subject of a 2019 award-winning documentary, Jim Allison: Breakthrough. Dr. Allison, of the University of Texas MD Anderson Cancer Center, developed a way to unleash T cells (a type of white blood cell) to attack cancerous tumors, allowing one’s immune system to fight cancer. The invention of the first “immune checkpoint blockade” therapy earned him the 2015 Lasker Award and the 2018 Nobel Prize in Physiology or Medicine, among many other awards. For someone who originally did not set out to study cancer, his contributions to the field of immunotherapy have saved countless lives and pushed the frontiers of our knowledge of both cancer and the immune system.

Dr. Steven Rosenberg

Developed the first human cancer immunotherapy

Raised by Jewish immigrants from Poland, then 6-year-old Dr. Steven Rosenberg watched as his parents learned that many of their relatives had been killed in the Holocaust. Having witnessed “so much evil in the world,” he decided at an early age that he wanted to do something to help people. That desire later culminated in an idea: what if there was a way to activate a person’s immune system to attack and treat cancer without surgery or radiation? It’s a question that led Dr. Rosenberg to begin developing the first immunotherapy in 1976, though it took until 1984 and his 67th patient to confirm his hypothesis, resulting in the first FDA-approved human cancer immunotherapy. More than 30 years later, that 67th patient is still in great health, having effectively been cured of her widespread melanoma.

Accelerating Our Understanding of Cancer into the Future

From left, Drs. Mary-Claire King, Francis Collins, John Carpten, Ashani Weeraratna, Candelaria Gomez-Manzano, and Juan Fueyo.

Credit: National Cancer Institute, National Institutes of Health, Copyright held by, and used with permission of, The Board of Regents of the University of Texas System through The University of Texas MD Anderson Cancer Center

Dr. Mary-Claire King

Proved the existence of BRCA1, a gene that can cause breast and ovarian cancer

As a young assistant professor, Dr. Mary-Claire King began studying families devastated by breast cancer. The genetics of these families led her to BRCA1—a gene that can have inherited mutations that cause breast and ovarian cancer. It took 17 years for her to prove the existence of BRCA1, and now, 47 years after enrolling her first study participants, Dr. King continues to shed light on inherited cancers. As an accomplished geneticist and human rights activist, she also developed—with the Grandmothers of the Plaza de Mayo—genealogical matching to reunite kidnapped children with their families in Argentina, as well as the first use of DNA sequencing to identify victims of the Argentinian “Dirty War.” Her current research interests include inherited breast and ovarian cancer, and genetics of severe mental illness and immunological disorders in children.

Dr. Francis Collins

Led the sequencing of the human genome as well as the mapping of 33 cancer types at a molecular level

The word “genomics” was only recently coined in 1980, and Dr. Francis Collins has been involved in its study since the beginning. Dr. Collins grew up on a farm, the son of a drama professor father and playwright mother—the latter of whom taught him at home before he started going to school in 6th grade. Driven by the thrill of discovery and motivated to help people, he became a physician and geneticist. Known for his leadership of the international Human Genome Project, which sequenced the entire human genome in 13 years, and The Cancer Genome Atlas, which mapped 33 cancer types at a molecular level, Dr. Collins is also highly regarded for his discoveries of various disease genes. Serving as NIH director since 2009, he still manages to run a prolific lab, studying diseases such as progeria and diabetes, play guitar and piano, and ride his motorcycle.

Dr. John Carpten

Led first genome-wide scan for prostate cancer susceptibility genes in African-American people

Dr. John Carpten has spent a lot of his career understanding which cancers disproportionately affect underserved minorities and other communities, and why. He has spearheaded several high-impact studies in prostate cancer, myeloma, and breast cancer. He also conceived the African American Hereditary Prostate Cancer Study Network, which led to the first genome-wide scan for prostate cancer susceptibility genes in African-American people. Not only is he determined to reduce cancer disparities and increase minority representation in clinical trials and precision medicine studies, he’s also a dedicated mentor for the next generation of cancer researchers. Another doctor, Melissa Davis, described him as a “big brother” to all of the minorities in molecular sciences while he was at The Ohio State University. There, he organized support groups and facilitated networking for minority students, encouraging them to excel.

Dr. Ashani Weeraratna

Reshaped clinical practice with research findings on age-related differences in cancer treatment response

Bloomberg Distinguished Professor Dr. Ashani Weeraratna found that there are age-related differences in how people respond to certain cancer treatments—a groundbreaking finding now reshaping clinical practice. As a skin cancer researcher, she has also led public health initiatives to install sunblock dispensers throughout Philadelphia and to teach children about the dangers of sun exposure. A Sri Lankan who grew up in Lesotho in southern Africa before emigrating to the United States, Dr. Weeraratna is a fierce advocate for the contributions of immigrant scientists and has spoken passionately about her experiences with racism and harassment in this country, and about her belief in the American Dream. She is also a champion of and mentor for junior faculty, women, and people of color in science.

Dr. Candelaria Gomez-Manzano and Dr. Juan Fueyo

Created a new therapy that uses a common cold virus to attack brain tumors

Husband and wife duo Drs. Candelaria Gomez-Manzano and Juan Fueyo created an experimental therapy that harnesses a common cold virus and transforms it into something that can attack glioblastoma—the most common and deadly of brain tumors. This so-called “smart bomb virus” is an immunotherapy that has the potential to destroy these tumors without radiation or chemotherapy. Both Drs. Gomez-Manzano and Fueyo are neuro-oncology professors who emigrated to the United States from Spain and work side by side in their laboratories at the University of Texas MD Anderson Cancer Center in Houston.

Immunotherapy to Treat Cancer

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Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. The immune system helps your body fight infections and other diseases. It is made up of white blood cells and organs and tissues of the lymph system.

Immunotherapy is a type of biological therapy. Biological therapy is a type of treatment that uses substances made from living organisms to treat cancer.

As part of its normal function, the immune system detects and destroys abnormal cells and most likely prevents or curbs the growth of many cancers. For instance, immune cells are sometimes found in and around tumors. These cells, called tumor-infiltrating lymphocytes or TILs, are a sign that the immune system is responding to the tumor. People whose tumors contain TILs often do better than people whose tumors don’t contain them.

Even though the immune system can prevent or slow cancer growth, cancer cells have ways to avoid destruction by the immune system. For example, cancer cells may:

  • Have genetic changes that make them less visible to the immune system.
  • Have proteins on their surface that turn off immune cells.
  • Change the normal cells around the tumor so they interfere with how the immune system responds to the cancer cells.

Immunotherapy helps the immune system to better act against cancer.

What are the types of immunotherapy?

Several types of immunotherapy are used to treat cancer. These include:

  • Immune checkpoint inhibitors, which are drugs that block immune checkpoints. These checkpoints are a normal part of the immune system and keep immune responses from being too strong. By blocking them, these drugs allow immune cells to respond more strongly to cancer.Learn more about immune checkpoint inhibitors.
  • T-cell transfer therapy, which is a treatment that boosts the natural ability of your T cells to fight cancer. In this treatment, immune cells are taken from your tumor. Those that are most active against your cancer are selected or changed in the lab to better attack your cancer cells, grown in large batches, and put back into your body through a needle in a vein.T-cell transfer therapy may also be called adoptive cell therapy, adoptive immunotherapy, or immune cell therapy.Learn more about T-cell transfer therapy.
  • Monoclonal antibodies, which are immune system proteins created in the lab that are designed to bind to specific targets on cancer cells. Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system. Such monoclonal antibodies are a type of immunotherapy.Monoclonal antibodies may also be called therapeutic antibodies.Learn more about monoclonal antibodies.
  • Treatment vaccines, which work against cancer by boosting your immune system’s response to cancer cells. Treatment vaccines are different from the ones that help prevent disease.Learn more about cancer treatment vaccines.
  • Immune system modulators, which enhance the body’s immune response against cancer. Some of these agents affect specific parts of the immune system, whereas others affect the immune system in a more general way.Learn more about immune system modulators.

Which cancers are treated with immunotherapy?

Immunotherapy drugs have been approved to treat many types of cancer. However, immunotherapy is not yet as widely used as surgery, chemotherapy, or radiation therapy. To learn about whether immunotherapy may be used to treat your cancer, see the PDQ® adult cancer treatment summaries and childhood cancer treatment summaries.

What are the side effects of immunotherapy?

Immunotherapy can cause side effects, many of which happen when the immune system that has been revved-up to act against the cancer also acts against healthy cells and tissues in your body.

Learn more about immunotherapy side effects.

How is immunotherapy given?

Different forms of immunotherapy may be given in different ways. These include:

  • Intravenous (IV)
    The immunotherapy goes directly into a vein.
  • Oral
    The immunotherapy comes in pills or capsules that you swallow.
  • Topical
    The immunotherapy comes in a cream that you rub onto your skin. This type of immunotherapy can be used for very early skin cancer.
  • Intravesical
    The immunotherapy goes directly into the bladder.

Where do you go for immunotherapy?

You may receive immunotherapy in a doctor’s office, clinic, or outpatient unit in a hospital. Outpatient means you do not spend the night in the hospital.

How often do you receive immunotherapy?

How often and how long you receive immunotherapy depends on:

  • Your type of cancer and how advanced it is
  • The type of immunotherapy you get
  • How your body reacts to treatment

You may have treatment every day, week, or month. Some types of immunotherapy given in cycles. A cycle is a period of treatment followed by a period of rest. The rest period gives your body a chance to recover, respond to the immunotherapy, and build new healthy cells.

How can you tell if immunotherapy is working?

You will see your doctor often. He or she will give you physical exams and ask you how you feel. You will have medical tests, such as blood tests and different types of scans. These tests will measure the size of your tumor and look for changes in your blood work.

What is the current research in immunotherapy?

Researchers are focusing on several major areas to improve immunotherapy, including:

  • Finding solutions for resistance.
    Researchers are testing combinations of immune checkpoint inhibitors and other types of immunotherapy, targeted therapy, and radiation therapy to overcome resistance to immunotherapy.
  • Finding ways to predict responses to immunotherapy.
    Only a small portion of people who receive immunotherapy will respond to the treatment. Finding ways to predict which people will respond to treatment is a major area of research.
  • Learning more about how cancer cells evade or suppress immune responses against them.
    A better understanding of how cancer cells get around the immune system could lead to the development of new drugs that block those processes.
  • How to reduce the side effects of treatment with immunotherapy.
Find more information about immunotherapy clinical trials near you HERE.

Immunotherapy to Treat Cancer was originally published by the National Cancer Institute.