Najem A, et al. – This study examines the downstream microphthalmia associated transcription factor (MITF) targets that can explain this anti–apoptotic effect and assess in parallel the effect of p53 reactivation on the promotion of apoptosis under MAP kinase kinase (MEK) inhibition in a panel of Q61NRAS–mutant melanoma cells. In this study, MITF/Bcl–2 has been determined as a key mechanism underlying resistance of neuroblastoma RAS viral oncogene homolog (NRAS)–mutant melanoma cells to apoptosis by MEK inhibitors. It paves the way for a promising drug combination that could prevent or reverse anti–MEK resistance in this group of patients.