Metformin: A Potential Chemosensitizing Agent for Improving Castration-resistant Prostate Cancer Treatment

Symptomatic metastatic castration-resistant prostate cancer (CRPC) is treated with docetaxel chemotherapy which provides a survival benefit but is associated with significant toxicity. A novel therapeutic approach is combining docetaxel with an agent that enhances its efficacy (i.e. a chemosensitizer). Metformin, an oral biguanide used to treat Type 2 diabetes, has been shown to have anti-neoplastic activity, and more specifically, enhance the effect of chemotherapy in multiple types of solid tumors. We hypothesized that metformin would act as a chemosensitizing agent when combined with docetaxel chemotherapy in CRPC. A retrospective cohort study of CRPC patients in Ontario indicated metformin did not have a chemosensitizing effect. However, in vitro experiments completed using CRPC cells indicated metformin may act as a chemosensitizing agent when combined with docetaxel in PC3 cells but not in DU145 cells. Therefore, metformin may be a novel chemosensitizing agent for CRPC and further investigation of cellular mechanisms is warranted.M.Sc