Intriguingly, metformin, an old anti-hyperglycemic drug that demonstrates numerous extra-metabolic actions, was recently observed to enhance the antitumor activity of MEK-I in human LKB1-wild-type NSCLC cell lines, independently of KRAS mutational status, through downregulation of the GLI Family Zinc Finger 1 (GLI1) and reduction of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)-mediated transcription of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) [44]. This evidence concerns the gene KRAS and non-small cell lung carcinoma.