Mechanistically, this drug resistance depends in large part on a gain in the activity of the rate-limiting enzyme of the NAD+ salvage pathway Nicotinamide Phosphoribosyl Transferase (NAMPT) that fuels mitochondrial OXPHOS, and that was previously identified as a driver of melanoma targeted therapy resistance [22, 23], but never shown to be negatively regulated by mTORC2. Here, NAMPT is linked to melanoma.