title: Targeting metabolic reprogramming as a potential therapeutic strategy in melanoma.
abstract: Metabolic reprogramming is a recognized hallmark of cancer. In order to support continued proliferation and growth, tumor cells must metabolically adapt to balance their bioenergetic and biosynthetic needs. To achieve this, cancer cells switch from mitochondrial oxidative phosphorylation to predominantly rely on glycolysis, a process known as the "Warburg effect". The BRAF oncogene has recently emerged as a critical regulator of this process in melanoma, bringing to the fore the importance of metabolic reprogramming in the pathogenesis and treatment of metastatic melanoma. In this review, we summarize our current understanding of oncogenic reprogramming of metabolism in BRAF and NRAS mutant melanoma, and highlight emerging evidence supporting a metabolic basis for MAPK pathway inhibitor resistance and metabolic vulnerabilities that may be exploited to overcome this.
authors.affiliation: Molecular Oncology Laboratory, Oncogenic Signaling and Growth Control Program, Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia.
authors.forename: Lorey K
authors.initials: LK
authors.lastname: Smith
authors.affiliation: Molecular Oncology Laboratory, Oncogenic Signaling and Growth Control Program, Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia.
authors.forename: Aparna D
authors.initials: AD
authors.lastname: Rao
authors.affiliation: Molecular Oncology Laboratory, Oncogenic Signaling and Growth Control Program, Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia; Translational Research Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, Australia; Department of Pathology, University of Melbourne, Australia; Department of Medicine, St. Vincent's Hospital, University of Melbourne, Australia. Electronic address: grant.mcarthur@petermac.org.
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF(V600E); Melanoma; Metabolism; NRAS