Metformin and Angiogenesis in Cancer - Revisited.

Several clinical studies demonstrated that diabetic patients treated with metformin were less likely to develop vascular complications, independent of glycemic control. It was also demonstrated that the large variety of metformin's vascular actions can be seen in nondiabetic conditions. Metformin has an interesting potential to treat vascular dysfunction and tumor angiogenesis in conditions beyond diabetes. Since metformin's use in cancer as a single antiangiogenic agent appears to be a therapeutic disappointment, the use of the drug as part of combination anticancer modality represents a therapeutic challenge. The normalization of vascular dysfunction as a new therapeutic strategy may provide better delivery of conventional anticancer agents to the tumor and disrupted tumor environment. In this review, we will outline the available information from the literature regarding metformin and tumor angiogenesis and suggest eventual experimental and clinical approaches.