The potential mechanisms underlying the efficacy of MEK/Plk1 inhibitors combination therapy include enhanced CHK/p53 pathway, arrest of cells in both the G0/G1(induce by MEK inhibitor) and G2/M (induce by Plk1 inhibitor) phase, and eventually induction of apoptosis in NRAS‐mutant melanoma cell [287, 290]. This evidence concerns the gene TP53 and melanoma.