21 Oct Metformin May Be Protective Against Cancer
Medical Research: What are the main findings of the study?
Dr. Romero: There is increasing epidemiologic and preclinical data indicating that the commonly used diabetic drug, metformin, may have anticancer effects. In ovarian cancer, in 2011 in Obstetrics & Gynecology we reported that in a retrospective cohort ovarian cancer patients that were using metformin had increased survival compared to those not using mefomrin. In this study, we expand on those findings by testing whether metformin can prevent ovarian cancer or improve response to chemotherapy in mouse models.
In a prevention study, we found that mice treated with metformin before cancer was initiated developed less tumor than those treated with placebo. In a treatment study, in vitro, metformin increased the cytotoxic effect of paclitaxel. In addition, using a genetic mouse model we show that the combination of paclitaxel plus metformin results in a greater tumor reduction than either drug used alone.
Medical Research: What was most surprising about the results?
Dr. Romero: The molecular mechanism by which metformin protects against cancer is not entirely clear. An early hypothesis was that metformin activates AMPK, a critical regulator of metabolism in the cell. When activated AMPK inhibits energy-consuming processes such as fatty acid and protein synthesis, ultimately resulting in cell death. In this study, like others before us, we show that in ovarian cancer metformin activates AMPK and alters metabolism in the cancer cell.
In addition, we report two new effects of metformin in ovarian cancer:
First, metformin treatment reduced levels of several important receptor tyrosine kinases (RTKs).
Second, metformin inhibited expression of fatty acid binding protein 4 (FABP4). Metformin’s inhibition of FABP4 was particularly exciting as we reported in 2011 in Nature Medicine that FABP4 plays a key role in ovarian cancer metastasis.
Medical Research: What should clinicians and patients take away from your report?
Dr. Romero: Clinicians and patients should be aware of the increasing preclinical research indicating that metformin may have anticancer effects in several cancer types, including ovarian cancer. The protective effect of metformin has been reported in the context of prevention as well as adjuvant treatment. However, while promising, the findings to date do not include prospective clinical trial testing in patients and therefore do not justify use of metformin as a cancer treatment.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Romero: The study reported here adds to the sum of preclinical and epidemiologic data supporting the hypothesis that metformin may have a protective effect in ovarian cancer and prospective testing in patients is warranted. In fact, a randomized phase 2 clinical trial is ongoing at University of Chicago during which newly diagnosed ovarian cancer patients are treated with metformin or placebo plus standard chemotherapy. After completion of chemotherapy, patients will continue on metformin or placebo for two years and progression free survival will be evaluated (PI: S.D Yamada, NCT02122185).
American Journal of Obstetrics & Gynecology
Received: July 20, 2014; Received in revised form: September 25, 2014; Accepted: October 16, 2014; Published Online: October 19, 2014