期刊
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
卷 98, 期 -, 页码 192-201出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2019.05.001
关键词
Metabolic reprogramming; BRAF; NAD(+) metabolism; NAMPT; Melanoma; Combination therapy
资金
- Italian Institute for Genomic Medicine Institutional funds
- Gilead Fellowship program 2018
- Ministry of Education University and Research-MIUR, PRIN Project [2017CBNCYT]
- Progetto strategico di Eccellenza Dipartimentale [D15D18000410001]
- ITN INTEGRATA program [813284]
Cancer cells rewire their metabolism to support proliferation, growth and survival. In metastatic melanoma the BRAF oncogenic pathway is a master regulator of this process, highlighting the importance of metabolic reprogramming in the pathogenesis of this tumor and offering potential therapeutic approaches. Metabolic adaptation of melanoma cells generally requires increased amounts of NAD(+), an essential redox cofactor in cellular metabolism and a signaling molecule. Nicotinamide phosphoribosyltransferase (NAMPT) is the most important NAD(+) biosynthetic enzyme in mammalian cells and a direct target of the BRAF oncogenic signaling pathway. These findings suggest that NAMPT is an attractive new therapeutic target, particularly in combination strategies with BRAF or MEK inhibitors. Here we review current knowledge on how oncogenic signaling reprograms metabolism in BRAF-mutated melanoma, and discuss how NAMPT/NAD axis contributes to these processes. Lastly, we present evidence supporting a role of NAMPT as a novel therapeutic target in metastatic melanoma.
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