NAMPT as a therapeutic target in melanoma: linking NAMPT-dependent metabolic reprogramming and immune regulation

Targeted therapy and immune checkpoint inhibitors have improved treatment for BRAF-mutated metastatic melanoma patients, but resistance dramatically impacts survival. Complementary therapies are needed. BRAF inhibitor-resistant cells show increased NAD, supporting metabolic adaptations underlying drug resistance. Nicotinamide phosphoribosyltransferase (NAMPT) is a driver of resistance and progression, and its overexpression correlates with BRAF mutations. Indeed, our preliminary data suggest that NAMPT may have an unknown function in the nucleus and in regulating immune responses, potentially impacting immune checkpoint inhibitors.