Individualizing Chemotherapy using the Anti-Diabetic Drug, Metformin, as an “Adjuvant”: An Exploratory Study

Abstract

Cancer remains one of the most challenging diseases to treat in this new millennium. In an attempt to increase tumor response rates and decrease patient toxicity to various chemotherapeutic agents, the efficacy of metformin as a chemosensitizer was investigated. Preclinical and clinical evidence supports the use of metformin as a cancer therapeutic particularly in the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon, as metformin has the ability to lower circulating insulin levels. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by regulating cellular metabolism thereby reducing proliferation and inducing apoptosis. A variety of solid tumor single-cell heterogenates were incubated with chemotherapeutic agents, plus/minus metformin, and analyzed for cell-death. A total of fourteen solid-tumors of various types were studied; ten of the fourteen tumors (71%) exhibited poor or modest sensitivity to the chemo agents tested, but when metformin was combined, a synergistic effect was observed resulting in high sensitivity (high cell kill); one of the fourteen tumors (7%) exhibited a marginal sensitivity to metformin employed as a single agent. Our findings indicate a potential role for metformin in oncology therapeutics as a powerful adjuvant to chemotherapy in a wide range of cancer types.The diversity of the tumor specimens studied further validates the necessity to conduct clinical studies on the efficacy of metformin in the oncology setting. The clinical safety, wellcharacterized pharmacodynamic profile, and low cost of metformin make it an ideal candidate for development as an effective adjuvant anticancer agent. Nonetheless, a randomized controlled clinical trial must be designed to further correlate and validate this preliminary pilot study and to fully appreciate the impact of metformin on cancer recurrence and survival.