Metformin for non-small cell lung cancer patients: Opportunities and pitfalls

Despite exciting advances of the anticancer armamentarium in the recent years, mortality of non-small cell lung cancer (NSCLC) remains high and novel treatments are requisite. Therapy intensification is explored with promising, but expensive and potentially toxic new compounds. Repositioning already existing drugs for cancer treatment could save money and improve patient outcomes in specific contexts. Observational data suggest that use of the standard antidiabetic agent metformin decreases lung cancer incidence and mortality. Several basic researches have shown various anticancer effects of metformin, acting both on the glycolytic metabolism and on the tumoral immune microenvironment. Synergistic actions of metformin with antitumoral agents in preclinical NSCLC models have then been highlighted. Recent retrospective studies advocated improved outcomes in NSCLC diabetic patients receiving metformin with chemoradiotherapy or systemic compounds (including conventional platinum-based chemotherapy and EGFR tyrosine kinase inhibitors). Several prospective randomized trials are therefore currently assessing the addition of metformin to standard therapy in non-diabetic lung cancer patients. This article reviews promises and possible limitations of concurrent metformin used as an anticancer agent in NSCLC patients.