Lewis Cantley is a cell biologist and a professor in the Departments of Systems Biology and Medicine at Harvard Medical School. Among his research contributions are the discovery and study of the enzyme PI-3-kinase, now known to be important to understanding cancer and diabetes mellitus. He is also the Director of Cancer Research at the Beth Israel Deaconess Medical Center, in Boston, Massachusetts.
Dr. Siddhartha Mukherjee: As you mentioned there are some parts of the body, some tissues where cancer is more infrequent and other tissues where cancer is more frequent. Dr. Schrag, give us a sense of why cancer often occurs in certain tissues and rarely occurs in other tissues.
Dr. Deborah Schrag: You know we don’t know the answer to that. We do certainly know that lifestyle factors are extremely important and have an enormous influence in terms of where cancers occur, so we know that exposure to hormones and the hormonal environment that people are exposed makes an enormous difference. This is true for breast cancer, prostate cancer. These remain two of the most common cancers among men and women. Of course smoking is also- remains an important issue. Now we know that we can’t- if we could modify folks lifestyle factors we would not be able to eradicate cancer, but just as Dr. Varmus was talking about how there are certain commonalities, there are certain common molecular mechanisms that go awry frequently, certain key patterns. We also know that with respect to behaviors, lifestyle, exposure there is certain commonalities, not enough exercise, too many calories and we have to work to exploit these and we really have to work to understand the interactions between the molecular events at the cellular level and the environmental exposures and lifestyle choices people make and how these factors interact.
Dr. Harold Varmus: Could I just add one point to that? The question you raised about some organs not having cancers. For example, the heart, that is what I would call a provocative question. Why shouldn’t there be a cancer there and it leads you to think about what cells in any organ are at risk of cancers and it’s very likely that the incidence of cancer in different tissue types, prostate versus heart for example, virtually every adult male at the age of 90 having some prostate cancer and heart cancers being virtually unheard of probably reflects how many cells are at risk of becoming a cancer in any single organ and the likelihood that those cells are exposed to some kind of oncogenic stress, whether it’s tobacco smoke or hormonal influence such as Debbie is referring to, but to me the remarkable variation not just among organs, but among organ types in different environmental settings, different locations represent one of the great challenges that I don’t think the cancer community has completely grappled with yet and to me this is an area of provocative research that we ought to be paying more attention to now that we have better tools for looking at genetics.
Deborah Schrag: So an interesting example that comes up for me all that time that I just don’t understand. We’re all born with 25 feet of small intestine, but yet we see only fewer than 5,000 cases a year in the United States.
Siddhartha Mukherjee: Contrast that with the large intestine...
Deborah Schrag: We contrast that with colon cancer, which remains one of our top cancers. Well you know there is 6 to 9 feet of large bowel and we have 150,000 cases per year. When we look at these cells under the microscope it’s all epithelial cells. I mean an intestinal cell in the small intestine and in the large intestine is molecularly not that different. The large bowel cells are a little bit more engaged in reabsorbing water than they are in reabsorbing nutrients, but we do not understand why there is this dramatic difference between the incidence of cancer in the small bowel, which there is more of and the large bowel. We haven’t answered that.
Harold Varmus: It brings up a very interesting new theme in cancer research. What is the role of the microorganisms we carry around with us? What is now being called the microbiome and of course the large intestine has trillions of bacteria and the small intestine has much less. That may well be that that is a driver of oncogenic change and of course the small intestine tumors, many of which you- as you mentioned, there are some. They are very frequently sarcomas, that is cancers of connective tissue as opposed to being epithelial and that is a very interesting example of that contrast.