Characterizing metformin response and sensitivity biomarkers in breast cancer

Abstract

The anti-diabetic drug metformin has been shown to exhibit broad in vitro and in vivo anti-neoplastic activity in various cancer types, including breast cancer. Despite numerous clinical trials ongoing, no targeted biomarkers currently exist to predict or monitor patient response to metformin treatment. Our lab previously conducted quantitative proteomics on MDA-MB-231 triple-negative breast cancer cells conditioned to physiologically-relevant doses of metformin. In this study, I have aimed to evaluate the genes encoding the top 12 most up-regulated proteins for their potential use as metformin biomarkers. I have found that several genes may modulate metformin sensitivity in MDA-MB-231 cells in a glucose-dependent manner. Most notably, I have identified aldoketo reductase family 1 member C3 (AKR1C3) to be a novel metformin response marker and a modifier of metformin sensitivity in breast cancer via both up- and downregulation. AKR1C3 protein expression may also have some predictive value to estimate metformin response in vitro.