Taken together, our findings tempt us to conclude that the c-Jun/RHOB/AKT signaling axis is a synthetic lethal partner of BRAF-mutant, and potentially of NRAS-mutant, melanomas and to propose RHOB as a critical biomarker to predict patient's response to PLX4032 and to select those that would benefit of the combination with AKT inhibitors. This evidence concerns the gene NRAS and melanoma.