Three reports indicated that the effect of metformin on cancer cells does not require activation of AMPK: (1) in prostate cancer cells, downregulation of AMPK did not affect metformin action and mTOR inhibition [57]; (2) the activation of AMPK was not required for the antimelanoma action of metformin and the use of an AMPK inhibitor failed to restore viability in metformin-treated cells [88]; and (3) inhibition of glucose production following treatment with metformin occurred in both AMPK- and LKB1-deficient hepatocytes [58]. The gene discussed is MTOR; the disease is cancer.