Metabolic flexibility in melanoma: A potential therapeutic target

Seminars in Cancer Biology
Maria Rosaria RuoccoAlessandro Arcucci

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.

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Citations

Jan 21, 2020·Experimental Dermatology·Maja GrabackaKrzysztof Reiss
Jul 8, 2020·Experimental Dermatology·Konrad Kleszczyński, Markus Böhm
Jun 13, 2020·Frontiers in Oncology·Angelica AvaglianoAlessandro Arcucci
Nov 19, 2020·British Journal of Cancer·Prakrit R KumarMarc D Moncrieff
Jan 21, 2021·Biomedicines·Claudio TabolacciFrancesco Facchiano
Jan 21, 2021·Journal of Functional Morphology and Kinesiology·Elisabetta Della ValleFelice Sirico
Mar 18, 2021·European Biophysics Journal : EBJ·Anna SobiepanekTomasz Kobiela
Apr 4, 2021·International Journal of Molecular Sciences·Michele LaiMauro Pistello
Apr 20, 2021·Cancer Metastasis Reviews·Hendrik Hld VandyckVéronique Winnepenninckx
Jun 3, 2021·International Journal of Molecular Sciences·Veronica RomanoAlessandro Arcucci
Aug 5, 2020·Anti-cancer Agents in Medicinal Chemistry·Tasnim ZahanFarhadul Islam
Jul 25, 2021·Cancers·Angela LeoMaria Letizia Taddei

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