Metformin May Be Key to Preventing Colorectal, Other Cancers
Dr. Hawk, who is also the T. Boone Pickens Distinguished Chair for Early Prevention of Cancer at M.D. Anderson, cautioned against overinterpreting the results. The short duration and small study size should temper enthusiasm somewhat – as should the debate about whether ACF are indeed precursors of colorectal cancer and whether affecting them in any way eventually affects cancer risk.
“Frankly, the Japanese are very good at these ACF studies. And while they have been very reproducible in animal models, human results have been much more difficult to confirm. A number of American investigators have tried to replicate earlier Japanese ACF studies using aspirin, a known colorectal cancer chemopreventive agent, and have not been able to get the same results.”
It’s unclear whether the difference lies in the treatment time, study design, or even the basic differences between a homogeneous Japanese population and the typical heterogeneous American study group, Dr. Hawk said. “Whatever it is, whether the results can be reproduced is the most important question.”
While larger studies are necessary to discover the unknowns of metformin, he said, the drug already has a lot going for it terms of the known. “We have so much data on metformin, and it has such a strong track record of safety, that I believe it’s an agent worth exploring.”
A review co-released with the studies suggested that metformin may be a more effective chemopreventive agent in patients with hyperinsulinemia. “There is evidence indicating that the growth of untransformed epithelial cells and a subset of cancers is stimulated by insulin, and that the systemic insulin-lowering action of metformin might inhibit the proliferation of these cancers,” wrote Dr. Michael Pollak of McGill University and Jewish General Hospital, Montreal. Cancers stimulated by insulin include endometrial, cervical, breast, and prostate cancers, as well as lung and colorectal malignancies. “This action of metformin shares mechanistic features with the manner by which caloric restriction inhibits the growth of certain cancers,” he said (Cancer Prev. Res. 2010;3:1060-5).
If Dr. Pollak’s theory is correct, Dr. Hawk said, metformin or other biguanides may help stem the flood of obesity- and diabetes-related cancers that researchers have predicted for several years. A recent study concluded that obesity could soon become the leading cause of cancer in women – possibly overtaking smoking as the leading cause (Int. J. Cancer 2010;126:692-702).
“The rise of diabetes-related cancer speaks to the importance of pursuing this investigation vigorously,” Dr. Hawk said. “We know that this is a problem of enormous impact for our future.”
Dr. Hosono, Dr. Dennis, and Dr. Hawk had no financial declarations. Dr. Pollak disclosed that he is a consultant for Merck, Novo Nordisk, Pfizer, and Sanofi-Aventis.
