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 BRAF^V600E 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.

In this review article, we describe the regulation of melanoma metabolic alterations and the metabolic interactions between cancer cells and microenvironment that influence melanoma progression and immune response. Finally, we summarize the hallmarks of melanoma therapies and we report BRAF/MEK pathway targeted therapy and mechanisms of metabolic resistance.

皮肤黑素瘤（CM）代表最具转移性和耐药性的实体瘤之一。CM的特征是非凡的代谢可塑性以及致癌激活与高能代谢之间的重要联系。实际上，黑色素瘤细胞可以在癌症进展过程中同时利用胞质和线粒体区室产生三磷酸腺苷（ATP）。但是，CM的能量需求主要取决于糖酵解，其上调与BRAF ^V600E影响的BRAF / MAPK途径的组成性激活密切相关激酶突变体。此外，黑色素瘤令人印象深刻的代谢可塑性允许开发对BRAF / MEK抑制剂（BRAFi / MEKi）的耐药机制并适应微环境变化。黑色素瘤细胞与肿瘤微环境之间的代谢相互作用影响免疫反应和CM生长。

在这篇综述文章中，我们描述了黑色素瘤代谢改变的调节以及癌细胞和微环境之间的代谢相互作用，这些相互作用影响黑色素瘤的进展和免疫反应。最后，我们总结了黑色素瘤治疗的特点，并报告了BRAF / MEK途径靶向治疗和代谢抗性机制。