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 mitochondri...

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Bibliographic Details
Published in:Seminars in cancer biology 2019-12, Vol.59, p.187-207
Main Authors: Ruocco, Maria Rosaria, Avagliano, Angelica, Granato, Giuseppina, Vigliar, Elena, Masone, Stefania, Montagnani, Stefania, Arcucci, Alessandro
Format: Article
Language:English
Subjects:
Animals
Cutaneous melanoma
Disease Progression
Disease Susceptibility
Energy Metabolism - drug effects
Glycolysis
Humans
Melanoma - drug therapy
Melanoma - etiology
Melanoma - metabolism
Melanoma - pathology
Metabolic alterations
Mitochondria - drug effects
Mitochondria - genetics
Mitochondria - metabolism
Molecular Targeted Therapy
OXPHOS
Therapeutic strategies
Treatment Outcome
Tumor Microenvironment - drug effects
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Summary: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. 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.
ISSN:1044-579X
1096-3650
DOI:10.1016/j.semcancer.2019.07.016