Metformin potentially exerts its anti-cancer activity by altering neoplastic cellular energy metabolism in an AMPK (adenosine monophosphate-active protein kinase) -dependent or an AMPK-independent signaling pathway,3 inhibiting protein synthesis, stopping the cell cycle, decreasing blood insulin levels, improving glycaemic control and immune system, destroying cancer stem cells and reducing the inflammatory response.4,5 These laboratory evidence yielded rationale for clinical studies to advance on investigating the role of metformin in survival for many site-specific cancers, including LC. This evidence concerns the gene INS and cancer.