Metformin: A Diabetes Drug for Cancer, or a Cancer Drug for Diabetics?

Clinical evidence that diabetics receiving metformin have a re-duced lifetime incidence of cancer1,2 has sparked keen interest in the biguanide class of compounds as potential anticancer agents. In Jour-nal of Clinical Oncology, Bonnani et al3 report on how presurgical treatment of patients with breast cancer with metformin affects the proliferation of their tumor cells. Their results highlight both the complexities and possibilities of metformin in breast cancer and, im-portantly, provide a rationale formoving to large-scale clinical trials to identify which patients are likely to benefit. The precise molecular target of metformin is unknown, but it acts to inhibit complex I of themitochondrial electron transport chain toblockoxidative respiration4 (Fig1).This results in increasedcellular AMP-to-ATP ratios and activates the AMP-activated protein kinase (AMPK).5 AMPK coordinates the activity of a plethora of key meta-bolic and growth pathways that together act to restore cellular energ