Richard L. Page: Randy, to start off our discussion, I’d say: Why cancer? What prompted you to devote your life to researching cancer and providing care to those who have it?
Randall Holcombe: Well,
I knew that I was going to be an academic physician. I was interested in science. And what really turned me on was immunology and the immune system. And as I went through residency training, I had thoughts of perhaps focusing on rheumatology or
infectious disease or hematology and oncology. All of them seem to have some overlap with the immune system. And I really found taking care of cancer patients very fulfilling. And that’s what led me in the direction of hematology-oncology.
RLP: And what about the immune system was exciting for you?
RH: Its complexity. At the time, we didn’t understand very much about the immune system. We didn’t know how to modulate it effectively. I thought there was a lot of opportunity for research to improve our understanding
of what was really a critical but not well-understood component of the human systems. I love that challenge.
RLP: Complexity is attractive.
RH: Absolutely. It stimulates thinking. And I think that’s what we should do as physician-scientists. We should think and solve problems.
RLP: And immunology, especially seemed like a “black box” back then, and the great challenge was sorting it out.
RH: Now we know a lot more. And now, it’s become a mainstay of treatment for patients with cancer and hematologic disorders. So that knowledge that people have gained over the last 40 years has now led to breakthrough
therapies for the patients that I see every day.
RLP: That’s interesting. You liked immunology, initially in its relationship to infectious disease, but you decided to pursue hematology/oncology when it became clear that immunology might help us treat cancer.
RH: When I began my work, there was a relatively small number of people working on the immunology and cancer connection. They were a minority that was shunned by most oncologists and hematologists. But I thought there was something
to it—that it was an area that I thought would be interesting to study. It led to some research projects that were focused on the immunology of cancer. We were using an immunostimulatory agent at the time for patients with colon cancer.
And I set up a clinical trial, which I had the fortunate opportunity to be able to do nationally through the Southwest Oncology Group, studying the immunologic response for patients receiving this medication. And it was a good start, I think,
to my career.
RLP: And the gastro-intestinal aspect that you’re now well known for, was your engagement serendipity—since there was a GI immunologic cancer study going on that sent you in that direction?
RH: Essentially, yes. I was initially trained as a hematologist, not an oncologist. Now, I practice as a gastrointestinal oncologist. But I was studying immunology in my laboratory. I had a K23 award from the NIH to support
my research activities. And that was focused on immunology. Then I started doing immunology for colon cancer patients. And, essentially, I was then told that I would be the colon cancer doctor because there was not another colon cancer doctor
around, and I must know something about colon cancer, because I
was doing laboratory research related to it. So I became a GI oncologist at that time.
RLP: And that’s a perfect combination of being attracted to a field and then finding how to grow and develop within it.
RH: And I think as a junior faculty member, you shouldn’t be too rigid about what you want to study. Because sometimes there are opportunities that are just slightly outside of what you thought you were going to focus
on, and those are opportunities that you have to seize, and you have to go with them. And that’s just how it turned out for me.
RLP: In more recent years you’ve been involved in non-basic research.
How did you make that transition to the work you do now?
RH: Well, again, that’s something that just sort of happened. I ran a lab as what you would call a traditional physician scientist for about 30 years. And I studied signaling pathways related to colon cancer in the laboratory. I think we did a good job. We had a number of different funding mechanisms to help support our work. We published lots of papers. And when I went to Mount Sinai Medical Center, I was put in charge of the clinical cancer program in addition to running my lab. I had two jobs—a clinical leadership job as well as a laboratory focus.
And as I became more and more involved in the delivery of cancer care, that’s what I got excited about. I started writing grants related to health sciences research, focused on cancer care delivery. One day I was sitting in my office and I had two grants to write. One was related to the lab research, and one was related to the health services research that I was doing. And I kept writing the latter, the health services research grant, and I could never get around to going back to writing the lab grant.
I realized at that point that I just didn’t have the bandwidth to do both at the level of excellence. And so I made that decision to close my lab. It was a really difficult decision at the time, because it was an essential part of me. Then I went and obtained an MBA to help me in the efforts that I was directing related to the conduct of the cancer program on the clinical side of things at Mount Sinai.