Metformin and neoplasia: implications and indications.

Metformin has been shown to exert anti-neoplastic and chemopreventive activities in epidemiological and animal studies. This review article discusses the epidemiological studies and examines the possible mechanisms by which metformin exerts its anti-carcinogenic activities in breast, colon, ovarian, lung, and prostate cancers. We performed a systematic review of the clinical studies examining the anti-neoplastic activities of metformin and the potential mechanisms associated with these activities. Several observational and biological studies revealed a significant association between metformin and reduction in cancer incidence. The mechanisms by which metformin exerts these effects are unknown. This action may be mediated through activation of AMP-activated protein kinase (AMPK), inhibition of the mammalian target of rapamycin (mTOR) pathway, and inhibition of insulin like growth factors (IGFs), and many others. Further laboratory investigation and large, prospective population clinical trials are required to elucidate metformin anti-neoplastic and chemo-preventive actions.