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A Visit with Drs. Scheinberg and Hyman

David Scheinberg, MD, PhD, came to MSK more than three decades ago. Since then, he has developed eight therapeutic agents that led to human clinical trials.

David Hyman, MD, arrived at MSK in 2011. He soon gained prominence for his translational work in early-phase clinical studies. We sat down with these talented researchers for their historical perspectives—and a look forward.

Dr. Scheinberg: MSK has a long and successful history of drug development because of the deep culture at MSK in translating laboratory discoveries into new therapies for patients with cancer. Thirty-five years ago we were asking, how do we understand what drives a cancer cell? What are specific targets? How do we activate the immune system to fight cancer? We believed such questions would pave the way to discoveries and new treatments. And we were right.

Dr. Hyman: And then your lab developed specialized antibodies to treat acute leukemia—by activating the immune system. These are cellular therapies that can often be less toxic than chemotherapies. Today, doctors use them to treat a variety of cancers.

Dr. Scheinberg: Yes. We continue to evolve these targeted drugs because we can engineer them to almost any cancer, with less damage to normal cells, which you cannot do with chemotherapy. The journey from discovery and preclinical work to clinical trial is also swifter with these treatments. We can reach patients faster—and often more effectively.

Dr. Hyman: Another extraordinary advance has been our ability to sequence a cancer genome. I graduated from medical school in 2006 when sequencing was in its infancy and it was electrifying! This gave us the ability to identify the very mutations that drive cancer. We began to think about cancers not only as lung or colon cancers, but also as diseases harboring mutation A or B. One major focus of modern drug development is attempting to target these mutations.

Dr. Scheinberg: What is so impressive about these advances is that they have given us a new paradigm. You led the clinical studies of larotrectinib, a drug that targets one mutation in 17 different, mostly rare malignances. It was approved by the FDA in November 2018.

Dr. Hyman: It was the first drug approved based solely on a specific genetic change in a tumor and the first cancer therapy developed simultaneously in adults and children. Roughly four out of five patients respond positively and consistently to the drug. There is nothing more satisfying than giving patients who have really lost hope a treatment that can potentially change their lives [See patient story]. That is why I went into this field.

Dr. Scheinberg: There are still many challenges, though, which is why philanthropy is so important. There are new questions to explore to make the treatments better. Why, for example, does a targeted treatment work so well in one patient, but not in another whose cancer has the same mutation?

Dr. Hyman: Or how do we detect cancer earlier? Whether you work at MSK, or are treated by MSK, the research that philanthropy helps fund is consequential. We have more than 100 research labs, we are running 800 or more clinical trials. With collaborations that cross state and country borders—our impact on families is everywhere.