We tested the antiproliferative and pro-apoptotic effects of the metformin and MEK-I (pimasertib or selumetinib) combination in a panel of NSCLC cell lines harbouring wild type LKB1, which has been defined as a predictor of response to metformin activity [13] and, in this study, we demonstrated not only that the synergism is evident in all the cell lines tested irrespective of the mutational status of KRAS gene, but the addition of metformin is able to overcome the innate resistance to MEK-Is, also in those cells with KRAS mutation, such as H358 cell line. The gene discussed is KRAS; the disease is non-small cell lung carcinoma.