Metformin in lung cancer: rationale for a combination therapy.

INTRODUCTION: Metformin is a widely used antidiabetic drug, which also displays significant growth inhibitory and proapoptotic effects in several cancer models, including lung cancer, alone or in combination with chemotherapeutic drugs. AREAS COVERED: The role of metformin as a chemopreventive drug in lung cancer is still an object of debate as epidemiological studies have shown contrasting results. More preclinical data support its role as an adjuvant drug in the treatment of lung cancer, in combination with chemotherapy or targeted molecular drugs, although the complete mechanism of action of metformin is still unclear, and potentially may exert unexpected effects with contradictory clinical implications. EXPERT OPINION: Future perspective studies are required in nonsmall-cell lung cancer (NSCLC) patients to better investigate the effect of metformin action on the RAS/RAF/MAPK pathway and the best context in which to use metformin in combination with molecularly targeted agents.