Dr. Jill O’Donnell-Tormey On The Five Things You Can Do To Become More Resilient During Turbulent Times

This interview was originally published on Medium.com.

Cancer research is the only way to get to cancer cures, and the Cancer Research Institute is an example of a nonprofit organization whose singular dedication to advancing the science of immunotherapy is making a real impact that is saving more lives today.

Cancer is a horrible and terrifying disease. There is so much great information out there, but sometimes it is very difficult to filter out the noise. What causes cancer? Can it be prevented? How do you detect it? What are the odds of survival today? What are the different forms of cancer? What are the best treatments? And what is the best way to support someone impacted by cancer?

In this interview series called, “5 Things Everyone Needs To Know About Cancer” we are talking to experts about cancer such as oncologists, researchers, and medical directors to address these questions. As a part of this interview series, I had the pleasure of interviewing Jill O’Donnell-Tormey, PhD, CEO and director of scientific affairs at the Cancer Research Institute (CRI).

CRI is a global nonprofit organization dedicated to investing in the most promising areas of cancer immunotherapy research with the goal of harnessing the power of our own immune system to conquer and cure all cancers.

Dr. O’Donnell-Tormey joined the organization in 1987 as director of scientific affairs and began serving as its chief executive in 1993. During her tenure at CRI, she has helped to create catalytic and novel research programs that span the laboratory and the clinic. She has guided over $500 million in funding to these programs, which enable research and scientific discoveries that are changing the course of cancer treatment today.

Dr. O’Donnell-Tormey sits on the boards of The Staten Island Foundation where she serves as Secretary; The City University of New York (CUNY); and Coherus Biosciences, Redwood, CA. She also serves on the Cancer Immunotherapy Advisory Board of the Focused Ultrasound Foundation, Charlottesville, VA, and the Editorial Advisory Board of Immuno-Oncology Insights. In 1998, Dr. O’Donnell-Tormey was named one of Irish America magazine’s “Top 100” Irish Americans. She is the recipient of the 2002 Fairleigh Dickinson University Pinnacle Award, the highest honor bestowed on its alumni; the 2013 CRI-Frederick W. Alt Award for New Discoveries in Immunology; and the 2020 Tara Withington Public Service Award from the Society for Immunotherapy of Cancer (SITC).

Thank you so much for joining us in this interview series! Before we dive into the main focus of our interview, our readers would love to “get to know you” a bit better. Can you tell us a bit about your childhood backstory?

I grew up on Staten Island as the oldest of three girls. I attended an all-girl Catholic school, Notre Dame Academy, from kindergarten through high school. I was imbued with confidence that I could do anything I set my mind to. I graduated as valedictorian in 1973. I was the first person in my family to attend college. I later graduated summa cum laude from Fairleigh Dickinson University with a BS in chemistry followed by a PhD in cell biology from the SUNY Downstate Medical Center.

What or who inspired you to pursue your career? We’d love to hear the story.

I always loved the idea of science and experimentation. I grew up with chemistry sets and microscopes (all presents I requested) and forced my playmates to spend time in my basement doing experiments. I am not sure where this interest came from. My parents were not scientists or physicians. In college I did an internship in a lab and found my calling. This was my first exposure to real scientific inquiry. I realized I was good at asking questions, designing experiments with controls, and organizing protocols and procedures. In college I became a chemistry major because I felt at that time biology required rote memorization and less thinking. But I was always intrigued with pathology and disease, so after graduation I decided to focus on what was then a relatively nascent field, cell biology. It allowed me to combine my chemistry and mechanistic background with natural sciences. While I was in graduate school my mother was diagnosed with ovarian cancer. This is what turned my focus to cancer. As a postdoctoral fellow my cancer interest intersected with immunology.

This is not easy work. What is your primary motivation and drive behind the work that you do?

Since 1987, I have not worked in a laboratory. Instead, I have worked for 35 years at the Cancer Research institute, a nonprofit organization that supports cancer immunology research around the world aimed at developing effective immunotherapies for all cancers. While I never envisioned leaving the lab, my tenure at CRI has allowed me to interact with world-renowned scientists and physicians. Many have served as mentors as my knowledge of cancer and immunology has broadened. I have come to realize that I have had a much greater impact on the problem of cancer by leading CRI than I could have ever had working on my own and doing my own research. My motivation continues to be enabling outstanding scientific research to yield better treatments for all cancer patients.

What are some of the most interesting or exciting projects you are working on now? How do you think that might help people?

The scientists and projects that CRI funds are now asking the critical question of why some cancers and some patients respond to immunotherapy and others do not. This requires research focused on the complex interplay of cancer and the immune system that takes place within the tumor microenvironment and throughout the body. Research that marries basic biology discovery and human clinical investigation. Research that focuses on the mechanisms and pathways that control the function of a diverse group of immune cells that together orchestrate the recognition and destruction of cancer. Research that unravels the ways a tumor suppresses an immune response. Research that identifies the biomarkers of innate and acquired resistance to the immune system’s response to cancer. Research that identifies the extrinsic factors, such as genetics, metabolism, and the microbiome, that impact the cancer-immunity cycle and aid or abet a productive immune response against cancer.

For the benefit of our readers, can you briefly let us know why you are an authority about the topic of Cancer?

I have spent greater than 35 years directly involved in the scientific enterprise that is unraveling the secrets of the human immune system and how it can be harnessed to treat all cancers.

Ok, thank you for all of that. Let’s now shift to the main focus of our interview. Let’s start with some basic definitions so that we are all on the same page.

What exactly is cancer?

Cancer is a broad category of disease that encompasses as many diverse types and subtypes of cancer as there are different types of cells in the body. These diseases share common traits we have come to recognize as cancer, including uncontrolled growth, the ability of tumors to abnormally reshape their immediate environment to draw in blood and nutrients, resistance to normal cell death mechanisms, and the ability to spread beyond the primary tumor site into other organs (a process called metastasis). As our understanding of the immune system’s interaction with cancer has deepened, we also now recognize other, immunological traits common to many types of cancer, including the ability to suppress the anti-cancer immune response as well as to recruit other, tumor-promoting components of the immune system to aid immunosuppression and metastasis.

What causes cancer?

The most common causes of cancer are linked to a person’s genetic makeup, environmental factors like pollutants, behaviors including smoking, alcohol consumption, and diet, and related issues like obesity and sedentary lifestyles. Some viruses can also lead to cancer, such as human papillomavirus that contributes to cervical and other cancers, and hepatitis C that can lead to liver cancer and non-Hodgkin lymphoma. Chronic inflammation, where the immune system is in a hyperactive state over extended periods, can also contribute to cancer formation. More recently, scientists have confirmed that a person’s microbiome — the makeup of bacteria, fungi, and viruses that naturally live on and inside us — can influence patient responses to immunotherapy and may contribute both to cancer development or protection against cancer, depending on the composition of the individual’s microbiome.

Extreme stress is also thought to be a factor in cancer development, perhaps by exacerbating existing predispositions while also impairing our immune system’s ability to combat cancer, although this is an ongoing area of study. The lack or presence of certain genes including those that may have been inherited from one’s parents can increase a person’s cancer risk. Here, knowing one’s family history can be extremely valuable as there are numerous tests now available that can help identify genetic risk factors and may also inform future treatment strategies should a person develop cancer. Genes contain the blueprint for how our cells develop, function, and die. In addition to inherited genes, spontaneous genetic mutations can also lead to cancer. Mutations occur naturally as a matter of the trillions of cells in our bodies replicating every moment — there are many opportunities for something to go wrong in the process. Genetic mutations can also be caused by some of the lifestyle and environmental factors described above. In most people, these mutations are detected by our cells’ replication machinery, and either are repaired or eliminated by triggering the cell’s death. Some people who develop cancer have deficiencies in these gene repair mechanisms. Over time, as these mutations increase in number, cells can begin to exhibit the common characteristics of cancer noted above. On the other side of the equation, scientists like those funded by CRI are exploring how these mutations enable cancer to evade our immune system with the goal of developing new strategies to mobilize an effective anti-tumor immune response.

What is the difference between the different forms of cancer?

There are several broad categories that describe some of the basic characteristics of cancer, most usually tied to the type of cell from which the cancer originates. These include carcinomas that arise from the skin and tissues that cover or line internal organs; sarcomas that begin in connective or supportive tissues like bone, cartilage, fat, muscle, or blood vessels; leukemias, which are cancers of the body’s blood-forming tissues, such as bone marrow; lymphomas and myelomas, which are cancers of the immune system itself affecting white blood cells including granulocytes, monocytes, and lymphocytes as well as plasma cells; and central nervous system cancers that affect the brain and spinal cord. Beyond these large buckets are myriad types and subtypes based on the specific tissue origin (e.g., breast, colon, lung, etc.) as well as the individual patient’s tumor gene expression and the patient’s overall genetic profile. Some types of cancer are highly responsive to immunotherapy due to their location in the body, how the tumor structure is formed, how “foreign” the cancer appears to the immune system based on the number of mutations, and whether the tumor has developed ways to evade the immune system. For example, skin cancers caused by exposure to ultraviolet radiation or lung cancers caused by carcinogens found in cigarette smoke tend to have elevated levels of mutation (doctors refer to this as “tumor mutational burden”) and significant success, even cure-like responses, have been seen in patients with advanced stages of these types of cancers. Conversely, other types of cancer are much harder to treat with immunotherapy and this is an area of intense focus in the research field right now. Some cancers grow more quickly and spread more aggressively than others, while some tend to be slow growing and remain localized unless the disease progresses to advanced stages and begins to spread. Finally, as each patient is unique, and each person’s cancer is unique, individual experiences with cancer and response to treatment can vary widely. All these and other factors must be considered by health care professionals when formulating a patient’s treatment plan.

I know that the next few questions are huge topics, but we’d love to hear your thoughts regardless. How can cancer be prevented?

Inoculation with vaccines against viruses that can cause cancer is the most reliable way to prevent developing these cancers. Routine preventive tests like colonoscopies, mammograms, and PAP smears can also help detect problems such as polyps in the colon, masses in breast tissue, or lesions on the skin that can be removed with surgery or otherwise treated before becoming full-blown cancer. Lifestyle also can play a role in preventing cancer, such as eating a balanced, high-fiber diet, not smoking, avoiding drinking alcohol, getting enough sleep, and exercising, however it’s important to note that cancer can still arise despite adhering to healthy habits.

How can one detect the main forms of cancer?

Cancers can be detected in several different ways. The routine healthcare exams I mentioned in the previous answer have been shown to effectively catch cancer at earlier stages, improving outcomes for patients. Cancer is sometimes discovered by accident as part of another health checkup or procedure, such as X-rays, CT scans, dermatology visits, and bloodwork that reveal irregularities and require further examination. Biopsies are taken to microscopically confirm the presence of cancer. Additional tests may be done on the tumor tissue to determine any genetic factors that may better inform the patient’s prognosis and influence treatment decisions.

Cancer used to almost be a death sentence, but it seems that it has changed today. What are the odds of surviving cancer today?

Every patient is different and responds differently to treatment, but generally survival has improved overall thanks to preventive testing and advances in cancer immunotherapy in treating some of the deadliest cancers like lung cancer. In the United States alone, it is estimated that there are 18.1 million cancer survivors, and this number is expected to increase to 22.5 million by 2032, according to the National Cancer Institute, which also notes that nearly 70 percent of survivors have lived beyond five years since diagnosis and nearly half live beyond ten years. Today’s treatment regimens are more nuanced than those available thirty years ago. They may include combinations of immunotherapy with other forms of cancer treatment that enhance patient responses. As clinical discovery advances and we continue to find more answers to that central question — why do some patients respond to immunotherapy while others do not? — we can expect overall survival to continue to improve across many different cancer types.

Can you share some of the new cutting-edge treatments for cancer that have recently emerged? What new cancer treatment innovations are you most excited to see come to fruition in the near future?

Checkpoint blockade, CAR T cell therapy, bispecific antibody therapies, and treatments that target parts of the immune system beyond T cells are among the most exciting new developments in cancer immunotherapy over the past decade and emerging today. The first FDA-approved checkpoint blockade therapy, ipilimumab, entered standard of care for certain melanoma patients in 2011, and a host of new approvals have followed since. To make these and emerging immunotherapies more effective for more patients, CRI scientists are applying the very latest in genetic engineering and computational science to enhance these treatments while also conducting basic research that will yield new treatment strategies. Exciting complementary approaches combining these treatments are also showing progress in clinical trials. These include drugs that target specific genetic mutations, interrupt blood vessel formation around tumors, or alter tumors in a way that makes them more vulnerable to immune attack, for example. New applications of technologies like focused ultrasound in the context of cancer immunotherapy are also very promising as are advances in imaging technologies that can show in real time at a cellular level how patients are responding to immunotherapy. Diagnostics are also advancing, with CRI-funded studies under way to develop less-invasive blood-based “liquid” biopsies that may predict patient responses to immunotherapy.

From your experience, what are a few of the best ways to support a loved one, friend, or colleague who is impacted by cancer?

As part of CRI’s patient education programs, including our CRI Virtual Immunotherapy Patient Summits, available in English and Spanish, our “Cancer Immunotherapy and You” webinars for patients and caregivers, and our Immunotherapy Patient Story videos, we have heard from thousands of cancer patients sharing their experiences with immunotherapy. From these testimonials, emails, and audience questions, it is clear that the role of loved ones in helping patients navigate their cancer journey cannot be overstated. When facing an overwhelming cancer diagnosis, patients may often rely on family members or friends to research treatment options, take notes during doctor visits, and providing general support such as driving to and from appointments, cooking food, handling health insurance issues, and more. This is on top of providing love and support and reminding patients that life continues through and beyond cancer.

What are a few of the biggest misconceptions and myths out there about fighting cancer that you would like to dispel?

Many people don’t realize how much progress has been made in treating cancer over just the past ten years. The money being invested by government, industry, and nonprofits like CRI in basic and clinical research is producing breakthrough advances like immunotherapy that are transforming cancer treatment for millions of patients around the world. Donating to a charity like CRI that is focused on its scientific mission is a good way for people who want to support cancer research to make a meaningful impact on the lives of patients. There is also a lot of misunderstanding of what clinical trials are and how they can benefit patients. Common myths around clinical research include patients believing they will be made to feel like a test subject instead of a patient. In fact, clinical trials provide some of the best care and many patients feel that they are included as members of the research team. Patients might now also understand that their participation in trials is fully voluntary and that they can leave the study at any time. Others worry that the treatments may be dangerous. While the first stage of clinical testing is focused on safety and dosage of new drugs or new drug combinations, years of preclinical research underpin such studies along with a growing body of evidence from real-world application of these treatments, providing confidence that the risks of treatment are carefully understood before the first dose is given. Some highly experimental treatments, so-called “first-in-man” studies, do carry a greater risk but these potential adverse events are discussed with patients in detail before they enroll in a study. Later stage clinical studies present a much lower risk profile as more is known about how the treatment works in people.

Thank you so much for all of that. Here is the main question of our interview. Based on your experiences and knowledge, what are your “5 Things Everyone Needs To Know About Cancer? Please share a story or example for each.

1.) Cancer is not a death sentence. Millions of people are living ten, twenty, or more years beyond diagnosis. In fact, thanks to advances in research, cancer is increasingly becoming a chronic, treatable disease that can be managed over time or even sometimes cured.

2.) Immunotherapy is transforming the cancer treatment experience, giving millions of patients around the world each year better odds of living longer while also enjoying a better quality of life than other treatment types offer.

3.) Immunotherapy is different from chemotherapy and radiation in that it targets the immune system and helps it attack cancer rather than drugs or radiation that directly kill cancer cells. The immune system’s ability to “remember” past targets means the protection that immunotherapy can offer lives on in the patient, providing durable defense against cancer long after treatment has been discontinued.

4.) Cancer research is the only way to get to cancer cures, and the Cancer Research Institute is an example of a nonprofit organization whose singular dedication to advancing the science of immunotherapy is making a real impact that is saving more lives today. Donor support for the work of organizations like CRI is essential to keeping the momentum going and accelerating progress.

5.) Clinical trials are not only a lifeline for some patients who have exhausted other treatment options, but they are also increasingly being considered for patients who have responded to other treatments to reduce risk of recurrence, for example. Clinical discovery in immunotherapy is evolving from patients with very late-stage disease to those at earlier stages, too. Clinical trials not only offer some of the best cancer care and access to innovative cancer treatments, but they also advance the field as a whole to help many other patients who are facing now or will face a cancer diagnosis in the future.

You are a person of great influence. If you could start a movement that would bring the most amount of good to the most amount of people, what would that be? You never know what your idea can trigger. 

Increasing public literacy around immunotherapy and cancer research may help policymakers better understand the need to fund medical research. The COVID-19 pandemic demonstrated how important scientific research is to addressing major health crises. As more people live longer and their risk of cancer rises, there is an urgency to this work.

How can our readers further follow your work online?

The Cancer Research Institute website at www.cancerresearch.org is a valuable resource for patients and caregivers interested in learning about cancer immunotherapy and clinical trials. Our stories, videos, and patient education events are among some of the resources available there. CRI also provides a number of convenient options for those who which to support our work by donating to or fundraising on behalf of CRI.

Thank you so much for these insights! This was very inspirational, and we wish you continued success in your great work.