Abstract
Metformin is the most widely prescribed drug for type II diabetes. Diabetics maintained on metformin have decreased incidence of several types of cancer, including lung cancer, compared to diabetics maintained on other anti-diabetic drugs. This retrospective analysis has raised the possibility that metformin might be an effective chemopreventive agent. In diabetics, metformin decreases hepatic gluconeogenesis and decreases circulating levels of IGF-I and insulin. In certain tissues such as liver, muscle, and fat, metformin activates AMP-activated kinase and inhibits mTOR, a kinase whose activity is required for lung tumorigenesis in several mouse models. We previously showed that metformin in the drinking water inhibits tobacco carcinogen-induced lung tumorigenesis in a mouse model of lung cancer. Inhibition of tumorigenesis occurred at steady state levels of metformin easily achieved in humans, and the mechanism of action in lung tissues appeared independent of AMPK but dependent upon inhibition of IGF-I receptor-mediated signaling. This presentation will describe the efficacy of metformin in other mouse models of lung cancer, identify additional tissue-specific biomarkers for metformin that might have predictive value, and discuss the design of clinical prevention trials with metformin.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN03-03.
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