Some years ago, one of my best friends lost his wife to ovarian cancer. It was so sad to watch. Now another good friend has the disease. This is the deadliest of all gynecological cancers and there are 22,000 new cases a year in America. Ovarian cancer is the fifth most common type of cancer and gynecological cancer death in the United States. As with many cancers, we are making important progress in understanding the disease.
I have just put up a piece explaining the critical role of the master metabolic genetic switches mTOR and AMPK in chronic disease and aging. Ovarian cancer is no different. mTOR signaling pathways are persistently activated in most ovarian cancers and multiple different genes in the pathway may be involved. Inflammation (NFkB) is also part of this signaling that is persistently switched on. mTOR has an important role in inflammation activation. mTOR inhibitors are used in organ transplant patients to reduce organ rejection due to inflammation. These pathways are important in developing resistance to initial chemotherapy in ovarian cancer. Higher mTOR activation is associated with a poor prognosis. It is responsible not only for the aggressiveness of ovarian cancer, but also contributes to resistance to the standard chemotherapy, cisplatin and paclitaxel.
Metformin directly inhibits mTOR and activates AMPK which accounts for most of the other metabolic effects of metformin. Diabetics who take metformin lower their risk of developing ovarian cancer by one third. Metformin improves the impact of chemotherapy and prolongs survival. Overall survival in ovarian cancer patients is 138 months (11.5 years) among diabetic patients on metformin compared to 35 months (almost 3 years) in the non-metformin group. Most patients were on standard chemotherapy. That is a 4-fold difference in survival. If I had ovarian cancer, I would take metformin. It is inexpensive, safe, and we have long-term experience with it. The benefits of metformin here probably are related to its impact on mTOR and AMPK and less about lower glucose levels.