Strikingly and similarly, p53 reactivation by APR-246 also broke intrinsic and acquired resistance and synergized with the MEK inhibitor pimasertib to induce massive apoptosis in NRAS-mutant melanoma cells with wild-type or mutant-p53, identifying MITF/Bcl-2 as a key mechanism underlying resistance of mutant-NRAS melanoma cells to apoptosis by MEK inhibitors and propose clinically relevant drug combinations able to prevent or reverse it [64]. Here, NRAS is linked to melanoma.