When the American Society of Clinical Oncology met in Chicago this spring, one of the hottest topics was the promise of immunotherapy against cancer. And one of the point men for the media was Roy S. Herbst, M.S. ’84, Ph.D., M.D., chief of medical oncology at Smilow Cancer Hospital, associate director for translational research, and Ensign Professor of Medicine, who appeared on CNN, Fox News, and in newspapers from as far away as South Africa and the United Kingdom. He has spent more than 20 years both in the lab, studying the underlying science of cancer, and in the clinic, bringing novel treatments to patients. He shares his colleagues’ excitement about immunotherapy, which harnesses the body’s immune system to fight tumors.
Even as a student at New Rochelle High School in New York, Herbst was interested in science. “I knew that I wanted to help people, and I always thought of medicine as a career.”
He came to Yale as an undergraduate, leaving in 1984 with both bachelor’s and master’s degrees summa cum laude. He earned a Ph.D. from The Rockefeller University in 1990 and an M.D. from Cornell in 1991. He completed his residency at Brigham and Women’s Hospital (BWH) in Boston and fellowships in oncology and hematology at Dana-Farber Cancer Hospital and BWH, and he received a master’s degree in clinical investigation from the Harvard-MIT clinical investigator training program. He then went on to the M.D. Anderson Cancer Center, where he led the lung cancer section for almost 10 years.
Five years ago he returned to the School of Medicine, where he had come as a Yale freshman to study biophysics and biochemistry. “I studied molecular biology and gave my master’s thesis defense in the conference room where we now have our developmental therapeutics seminar once a month,” he said. “The blackboard looks exactly the same.”
Why did you choose to devote your career to oncology?
At Cornell and Rockefeller, I was interested in science and medicine, and cancer seemed like an area where you could bring science to bear on difficult problems. In my second year of med school, my mother developed breast cancer. I remember taking her slides to the pathology group to confirm her diagnosis and exploring treatment options with my professors and mentor. This seemed like a natural area for me because of the pathology, the science, and the new therapies that were evolving. You could bring together the science and the caring for people all in one career.
Do you see yourself as a clinician or a scientist?
I see myself as someone who is looking to the lab for new ideas and new drugs, while serving on the front line of the clinical translation. I want to develop drugs that are safer and more effective for cancer patients by understanding why they work or why they don’t work. Every Tuesday I see patients at the Smilow hospital in the lung clinic, which I lead, and seek to implement the most novel protocol-driven care. I also maintain a small lab where we’re doing some basic translational studies, but we mostly collaborate with some of the top labs at Yale and elsewhere.
What is your role at Yale?
My primary goal is to make sure that medical oncology offers state-of-the-art care while building a grant-funded research program. As the chief of medical oncology I lead an ever-expanding group of medical oncologists with a robust clinical service. As the associate cancer center director for translational research, my team and I are working to enhance and build a grants infrastructure to do more to bring scientists into the study of cancer. We want to get more people working together on the common problem of how to better treat someone with an incurable cancer. There is so much expertise at Yale in basic science and clinical care, but the real trick is to get everyone working together to combat human disease. My real goal is not just the lung program. I need to see every program in the cancer center succeed in the same way.
Why has immunotherapy emerged as such a breakthrough?
What better than the specificity, memory, and adaptability of one’s own immune system to attack a cancer? It really is the identification of the immune checkpoint PDL1 and the establishment of PD1/PDL1 inhibitors that have changed the field. You have these tumors, and you would hope that the immune system’s T cells would recognize the tumor as foreign. But the tumor makes a protein, PDL1, which camouflages the tumor, making it invisible. The new therapies are trying to knock down that PDL1. A lot of this work, by the way, comes from the studies of Lieping Chen here at Yale. Patients with lung cancer who previously would succumb to their disease within a year are now alive at two, three years or more. We are seeing tumors shrink more than 20 percent of the time in lung cancer, 25 percent of the time in melanoma, and 15 percent of the time in renal cancer. These agents are benefiting people, but it’s not a home run. Only 20 to 25 percent of patients benefit. We clearly have to do better, and current work is aimed at identifying biomarkers of response and resistance so we can develop even more effective combinations.
What are the next steps?
One of our big initiatives at Yale is to collect tumor samples from patients who have responded to immunotherapy and from those who have not. We are performing immunopathology, sequencing tumors to understand what it is about those that respond versus those that don’t respond. The tumor can, unfortunately, learn how to become resistant. The immune system has memory; and hopefully, as the tumor adapts, the immune system also adapts. In some cases this does not occur and hence we are developing even more new combinations among targeted therapies, vaccines, and other immunotherapies.
How did you become one of the public faces of ASCO?
Our medical oncology section, led by Mario Sznol, Harriet Kluger, and Scott Gettinger, did some of the earliest immunotherapy studies for cancer. I led one of the earliest Phase 1 trials in immunotherapy, which was published in Nature last year. Since my work has been focusing on both the clinic and the science. I’m able to talk not just about the clinical results, but also about the science behind the results. And what good is your work if you can’t make people realize what you’re doing to help patients, to obtain grants, to encourage philanthropy and encourage other researchers to work with you?