As it has been demonstrated that the dimerization-driven transactivation of CRAF requires phosphorylation of the C-terminal 14-3-3 binding motif redundantly by AMPK and CRAF itself, we next investigated whether AMPKi blocks the RAF inhibitor–induced paradoxical activation of RAF–MEK–ERK signaling in Ras-mutated cancer cells, thus representing a viable combination strategy. This evidence concerns the gene RAF1 and cancer.