Metabolic flexibility in melanoma: a potential therapeutic target

Cutaneous melanoma (CM) represents one of the most metastasizing and drug resistant solid tumors. CM is characterized by a remarkable metabolic plasticity and an important connection between oncogenic activation and energetic metabolism. In fact, melanoma cells can use both cytosolic and mitochondrial compartments to produce adenosine triphosphate (ATP) during cancer progression. However, the CM energetic demand mainly depends on glycolysis, whose upregulation is strictly linked to constitutive activation of BRAF/MAPK pathway affected by BRAFV600E kinase mutant. Furthermore, the impressive metabolic plasticity of melanoma allows the development of resistance mechanisms to BRAF/MEK inhibitors (BRAFi/MEKi) and the adaptation to microenvironmental changes. The metabolic interaction between melanoma cells and tumor microenvironment affects the immune response and CM growth.