Metformin and pancreatic cancer: Is there a role?

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA, with a 5-year survival rate of 6 %. Anti-hyperglycemic treatments for type 2 diabetes mellitus that induce hyperinsulinemia (i.e., sulfonylureas) are thought to increase cancer risk, whereas treatments that lower insulin resistance and hyperinsulinemia (i.e., metformin) are considered cancer prevention strategies. Metformin is a cornerstone in the treatment of diabetes mellitus type 2. Retrospective studies have shown a survival benefit in diabetic patients with many solid tumors including pancreatic cancer that have been treated with metformin compared with patients treated with insulin or sulfonylureas. Metformin influences various cellular pathways, including activation of the LKB1/AMPK pathway, inhibition of cell division, promotion of apoptosis and autophagy, down-regulation of circulating insulin, and activation of the immune system. Ongoing research is redefining our understanding about how metformin modulates the molecular pathways implicated in pancreatic cancer. The authors review the topic critically and also give their opinion. Further studies investigating the effect of metformin in combination with chemotherapy, targeted agents, or radiation therapy are undergoing. In addition, the role of metabolic and other biomarkers is needed.