These AMPK-mediated activities, in addition toa potential tumorimmunogenic role for AMPK through indirect modulation of programmedcell death ligand 1 (PD-L1),44 supportedthe evaluation of metformin and other AMPK activators as anticanceragents in preclinical cancer models and even in several clinical trials.2,16 However, metformin and many of these AMPK activators have AMPK-independenteffects; therefore, the anticancer effects observed in these studiesmay not be directly attributed to increased AMPK activity. This evidence concerns the gene PRKAA1 and cancer.