Furthermore, we evaluated the potential value of the AMPKi against the paradoxical effect of RAF inhibitors in cancer therapy and demonstrated that the AMPKi could not only effectively block RAF inhibitor–induced activation of RAF–MEK–ERK signaling and cellular overgrowth in Ras-mutated cancer cells but also reduce the formation of drug-resistant clones derived from BRAFV600E-mutated cancer cells. The gene discussed is RAF1; the disease is cancer.