Metformin: from antidiabetic to cancer therapeutic
Abstract
Epidemiology studies have found that type 2 diabetics treated with metformin are at a lower risk for developing cancer. It was speculated that the lowered risk might be attributed metformin's indirect physiological effect of lowering blood insulin levels, which is the opposite of many other antidiabetic drugs. However, further study of metformin's mechanism of action at the cellular level helped develop an understanding of its effect on the individual cell. This helped show why, mechanistically, it makes sense to use metformin for the treatment of cancer. As an activator of AMP-activated protein kinase (AMPK) via inhibition of complex 1 of the mitochondrial electron transport chain, metformin causes suppression of tumor growth and cell cycle arrest by acting on the mTOR pathway and cyclin/CDKs, respectively. Metformin has been most extensively studied in breast cancer, showing great efficacy in numerous breast cancer cell lines that include ER positive, HER2 positive, and triple negative breast cancer cell lines. This compilation of data and results of metformin's efficacy in various cancer subtypes will help push metformin forward as a new chemotherapeutic for breast cancer, and eventually for other cancer types as well.
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