Dr Vinod P Balachandran & Dr Benjamin Greenbaum of Memorial Sloan Kettering Cancer Center On The 5 Things Everyone Needs To Know About Cancer
An Interview With Savio P. Clemente
Research and clinical trials are crucial. The more we know about cancer, the more prepared we will be to detect and treat it early, dramatically improving survival. Clinical trials, like the one we’re currently hosting for the pancreatic cancer mRNA vaccine, are paramount in determining whether new treatments are paying off.
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 Vinod P. Balachandran, MD and Benjamin Greenbaum, PhD of Memorial Sloan Kettering Cancer Center.
Dr. Vinod Balachandran is a surgical oncologist who specializes in treating people with both benign and cancerous diseases of the pancreas, bile duct, gallbladder, and liver.
Dr. Benjamin Greenbaum is an Associate Attending in the Computational Oncology Service at Memorial Sloan Kettering Cancer Center. Dr. Greenbaum’s research seeks to quantify the interaction of tumors with the immune system and to predict immune driven evolution of tumors and viruses. His work utilizes a broad range of tools, from statistical physics and information theory to evolutionary biology.
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?
Dr. Balachandran: I was heavily influenced by science in my childhood. My father was a physicist and my mother in pathology. This mix of quantitative science and biology is reflected in how I approach solving problems today.
Dr. Greenbaum: I heavily read encyclopedias and math and science books a lot as a child. I was inspired by the stories of physicists who turned theoretical insights into practical tools that changed everyday life, like lasers.
What or who inspired you to pursue your career? We’d love to hear the story.
Dr. Balachandran
I was fortunate to be mentored by several highly influential physician-scientists at Memorial Sloan Kettering — Ronald DeMatteo, Jedd Wolchok, Steven Leach, and many others. They showed me the enormous power of science to change the lives of cancer patients. I have tried to emulate them ever since.
Dr. Greenbaum
I am trained as a physicist and was inspired to study cancer biology and immunotherapy by Arnold Levine, Nina Bhardwaj, Taha Merghoub and Jedd Wolchok. I continue to be inspired by the incredible physician scientists and Memorial Sloan Kettering.
This is not easy work. What is your primary motivation and drive behind the work that you do?
Dr. Balachandran
I am inspired and driven by my interactions with pancreatic cancer patients and their families. The fact that pancreatic cancer outcomes remain dismal, motivates me to work hard to change this.
Dr. Greenbaum
There is a unique moment where it feels like we can really make an impact collectively and use scientific insights and approaches from multiple disciplines to change cancer care. Its motivating to feel such things are possible and help enable them.
What are some of the most interesting or exciting projects you are working on now? How do you think that might help people?
Dr. Balachandran: The COVID-19 pandemic caused incomprehensible suffering and loss of life over the last few years. But the silver lining in this ongoing tragedy is the rapid discovery and implementation of the highly effective COVID-19 vaccines, momentum which helped ratify several years of research and investigations — in our laboratory and many others — on personalized Messenger RNA (mRNA) vaccines. This success of the COVID vaccine has opened the door to many exciting areas in which similar mRNA technology might be applied, including importantly for fighting cancer.
As co-leaders of the Stand Up To Cancer®-Lustgarten Foundation Pancreatic Cancer Convergence Research Team, we are running the first clinical trial of a personalized mRNA vaccine for pancreatic cancer patients. This work predates the COVID epidemic but is now benefiting from increased interest and attention. And I have to say, Stand Up To Cancer works relentlessly to offer the newest, most effective and most promising cancer treatments to patients quickly by bringing together the best minds to collaborate, innovate and share cancer research. We credit much of our fruitful collaboration to the grants we have received from SU2C.
For the benefit of our readers, can you briefly let us know why you are an authority about the topic of Cancer?
Dr. Balachandran: I am a hepatopancreatobiliary surgeon, member of the immuno-oncology service of the Human Oncology and Pathogenesis Program, and a member of the David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center (MSKCC). I completed my B.S. in Physics at Cornell University, my MD at SUNY Stony brook, my General Surgery residency at Weill Cornell Medical Center, and my Complex Surgical Oncology fellowship at MSKCC. I performed my postdoctoral work in cellular tumor immunology, where I identified a new mechanism of action of T cell dependency of the anti-tumor effects of tyrosine kinase inhibitors in solid tumors and discovered new ways to synergize kinase inhibition with immune checkpoint therapy.
In addition to primarily caring for patients with pancreas cancer, I run an NIH-funded translational research laboratory with a primary objective to identify new immunotherapies for pancreatic cancer. I am the recipient of the Louise and Allston Boyer Young Investigator Award for Cancer Research, the Pershing Square Sohn Prize for Young Investigators, a Damon Runyon Clinical Investigator Award, a National Cancer Institute Cancer Moonshot Award, and a Stand Up to Cancer Phillip A. Sharp Innovation Award.
Dr. Greenbaum: I’m an Associate Member of Memorial Sloan Kettering Cancer Center in the Computational Oncology group. Our lab focuses on how the immune system effects the evolution of cancer and viruses, and we lead a programmatic effort in computational immuno-oncology. The goal of the later is to help understand responses to immunotherapies and enable new approaches. I have a PhD in theoretical physics from Columbia University and trained in the Theoretical Division of Los Alamos National Laboratory and the Simons Center for Systems Biology at the Institute for Advanced Study in Princeton.
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 is exactly cancer?
Dr. Greenbaum: Cancer is a group of diseases identified by the uncontrollable growth and spread of abnormal cells that can result in death if not treated.
What causes cancer?
Dr. Balachandran: Cancer is caused by certain changes to genes, the basic physical units of inheritance. There are many reasons the changes in genes might happen. Genes are arranged in long strands of tightly packed DNA called chromosomes. Cancer is a genetic disease that is caused by changes to genes that control the way our cells function, especially how they grow and divide. Although the causes of cancer development are not completely understood, a number of factors are known to increase risk, including many that are potentially modifiable (e.g., smoking and excess body weight, etc.) and others that are not (e.g., inherited genetic mutations, etc.). These risk factors may act simultaneously or in sequence to initiate and/or promote cancer growth.
What is the difference between the different forms of cancer?
Dr. Greenbaum: Each person’s cancer has a unique combination of genetic changes. As the cancer continues to grow, additional changes will occur. Even within the same tumor, different cells have different genetic changes. Cancer can affect any part of your body, and when it’s centralized to a specific location, we call it by that area of the body — i.e., pancreatic cancer affects the pancreas initially.
I know that the next few questions are huge topics, but we’d love to hear your thoughts regardless. How can cancer be prevented?
Dr. Balachandran: You can reduce your risk of getting cancer by making healthy choices like keeping a healthy weight, avoiding tobacco, limiting the amount of alcohol you drink and protecting your skin. Unfortunately, most pancreatic cancer cannot be prevented, but you can reduce your risk by maintaining a healthy weight, stopping any smoking and limiting alcohol intake. Other risk factors include pancreatitis and family history.
How can one detect the main forms of cancer?
Dr. Greenbaum: If a patient shows signs or symptoms of cancer, a healthcare provider might start by asking about their personal and family medical history and do a physical exam, as well as order any necessary labs and imaging tests, or a biopsy to help confirm a cancer diagnosis.
Cancer used to almost be a death sentence, but it seems that it has changed today. What are the odds of surviving cancer today?
Dr. Balachandran: Cancer survival is typically described in terms of relative survival, which is a measure of life expectancy among cancer patients compared to that of the general population of the same age, race and sex. Survival rates vary greatly by cancer type and stage, as well as the patient’s age at diagnosis. For example, according to the American Cancer Society, the average lifetime risk of pancreatic cancer is about 1 in 64, but each person’s chances are affected by certain risk factors. The five-year survival rate for pancreatic cancer is 10.8%.
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?
Dr. Balachandran: We met when Dr. Greenbaum won a 2016 SU2C® Sharp Award to study cancer immunotherapy with one of my colleagues at Memorial Sloan Kettering Cancer Center. We teamed up in 2017 to study what distinguishes long-term survivors of pancreatic cancer — the 9% who live more than five years after diagnosis — from other patients. We discovered that up to 12 years after recovering from cancer, survivors had specialized immune cells that recognized cancer proteins called neoantigens, findings that we confirmed in a subsequent follow up study. Based on this, we thought a vaccine might be able to coax the immune systems of all pancreatic cancer patients to recognize these neoantigens. The biggest challenge is that not all patients’ tumors have the same neoantigens.
Dr. Greenbaum: With these challenges in mind, our multi-disciplinary research team evaluates the feasibility of customized vaccines for cancer patients based on the combination of neoantigens present in each patient’s tumor. Our analytical approach, coupled with Dr. Balachandran’s immunological and clinical knowledge, helps us investigate the most effective way to create such personalized vaccines.
By modeling evolution at a few individuals who survive pancreatic cancer for long periods of time (5–12 years), we identified an initial set of high-quality neoantigens, or protein tags, on cancer cells that the immune system recognizes. We use computational approaches from statistical physics and machine learning to understand what makes a neoantigen high-quality. The goal is to develop a method for creating vaccines that will turn all pancreatic cancer patients into long term survivors.
In December 2019, our team launched a phase I clinical trial to test mRNA vaccines in pancreatic cancer — a full year before mRNA vaccines against COVID-19 became available. We’re excited to test if vaccines can eventually become a staple in the pancreatic cancer treatment plan.
Healing usually takes place between doctor visits. What have you found to be most beneficial to assist a patient to heal?
Defer this question.
From your experience, what are a few of the best ways to support a loved one, friend, or colleague who is impacted by cancer?
Dr. Balachandran: Before asking what your loved one may need or how you can help, be sure you can offer help in concrete, practical ways. Things like traveling to medical appointments, picking up medication or ensuring they keep up with things they loved prior to getting sick, will go a long way to offer support.
A patient’s mindset matters, too. You should always meet the person where they are in their journey. If your loved one is struggling with their diagnosis, don’t saturate them with positivity. Instead, meet them where they are and help them work toward acceptance. Simply being there is one of the best ways to support a loved one with cancer. Supporting someone with any serious illness can help them start to accept their situation and fully engage in their treatment plan.
What are a few of the biggest misconceptions and myths out there about fighting cancer that you would like to dispel?
Dr. Greenbaum:
“Pancreatic cancer is a silent killer.”
This is a common misconception fueled by an overall lack of awareness of signs and symptoms. There are signs and symptoms of pancreatic cancer that can seem vague or derivative of other illnesses; it can be easy to brush off indigestion, mid-back pain and weight loss. Knowing these are all symptoms of pancreatic cancer can save lives. By increasing awareness of the signs and symptoms of pancreatic cancer, more potentially life-saving treatment plans can be put into place.
“Pancreatic cancer is always deadly.”
Though pancreatic cancer accounts for about 3% of all cancers in the US and about 7% of all cancer deaths, pancreatic cancer can be treated if diagnosed early enough. If there is no sign that a tumor has spread beyond the pancreas, and you can physically undergo surgery, your doctors may decide to remove the tumor.
“Pancreatic cancer only affects men and older people.”
Pancreatic cancer affects both men and women, though it is slightly more common in men, according to the American Cancer Society’s 2022 statistics. The risk of developing pancreatic cancer goes up as people age. Patients are typically 45 years or older, and roughly two-thirds are at least 65 years old. As of 2022, the average age of diagnosis is 70.
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.
- We don’t know the cause of all cancers. For example, most pancreatic cancers are currently understood to be random, meaning they happen and we’re not sure why. It’s estimated that roughly 10% of pancreatic cancer diagnoses stem from genetic causes.
- There are many different types of cancers within each category of cancer. For example, pancreatic tumors can be exocrine or neuroendocrine. Adenocarcinoma is the most common and the most serious type of pancreatic cancer. The less common and more favorable prognosis is neuroendocrine tumor of the pancreas, also known as PNET. Other uncommon types include lymphoma and sarcoma of the pancreas.
- Research and clinical trials are crucial. The more we know about cancer, the more prepared we will be to detect and treat it early, dramatically improving survival. Clinical trials, like the one we’re currently hosting for the pancreatic cancer mRNA vaccine, are paramount in determining whether new treatments are paying off.
- Treatments and outcomes are improving! The typical pillars of a pancreatic cancer treatment plan are surgery, chemotherapy and radiation. The SU2C-Lustgarten Pancreatic Cancer Convergence Research Team is working on making the mRNA vaccine the mainstay of pancreatic cancer treatment.
- Where you get treatment matters!
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. :-)
Defer on this question.
How can our readers further follow your work online?
Dr. Balachandran and Dr. Greenbaum: You can keep up with our work with Stand Up To Cancer here, and on LinkedIn and Twitter (@bengrbm and @TheVinodLab).
Thank you so much for these insights! This was very inspirational and we wish you continued success in your great work.
