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.

Metabolic flexibility in melanoma: A potential therapeutic target / Ruocco, MARIA ROSARIA; Avagliano, Angelica; Granato, Giuseppina; Vigliar, Elena; Masone, Stefania; Montagnani, Stefania; Arcucci, Alessandro. - In: SEMINARS IN CANCER BIOLOGY. - ISSN 1044-579X. - 59:(2019), pp. 187-207. [10.1016/j.semcancer.2019.07.016]

Metabolic flexibility in melanoma: A potential therapeutic target

Ruocco Maria Rosaria
;
Avagliano Angelica;Granato Giuseppina;Vigliar Elena;Masone Stefania;Montagnani Stefania;Arcucci Alessandro
2019

Abstract

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.
2019
Metabolic flexibility in melanoma: A potential therapeutic target / Ruocco, MARIA ROSARIA; Avagliano, Angelica; Granato, Giuseppina; Vigliar, Elena; Masone, Stefania; Montagnani, Stefania; Arcucci, Alessandro. - In: SEMINARS IN CANCER BIOLOGY. - ISSN 1044-579X. - 59:(2019), pp. 187-207. [10.1016/j.semcancer.2019.07.016]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/757698
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