Molecular drivers of cellular metabolic reprogramming in melanoma

• Profound changes in cellular metabolism are a hallmark of melanoma.
• Rewiring of metabolism is controlled by known melanoma drivers.
• Metabolic changes in melanoma represent new targets for therapeutic intervention.
• Treatment effectiveness may depend on genetic drivers and mitochondrial performance.

The development of metastatic melanoma is accompanied by distinct changes in cellular metabolism, most notably a change in strategy for energy production from mitochondrial oxidative phosphorylation to cytoplasmic aerobic glycolysis. This bioenergetic switch occurs at the expense of less-efficient utilization of glucose, but is required for melanoma cells to meet their bioenergetic and biosynthetic demands. Recent work has implicated well-established melanoma drivers such as BRAF, PTEN, MITF, and ARF in the regulation of cellular energy metabolism. The metabolic changes in melanoma cells offer new opportunities for therapeutic intervention. However, inter- and intratumor bioenergetic heterogeneity caused by variation in genetic driver profiles and mitochondrial performance may impact on the effectiveness of treatment.