MTOR and neoplasm: If metformin merely acted as mTOR inhibitor, it should induce the same tumor resistance mechanisms as “classical” mTOR blockers (i.e. rapamycin), such as the relief of the mTOR/S6K1 negative feedback loop on IGFR-1/IRS-1, the activation of receptor tyrosine kinase-mediated intracellular pathways [15] and the loss of antiproliferative activity [16].