Abstract
Nicotinamide adenine dinucleotide (NAD+) is an important cofactor involved in many redox reactions. NAD+ serves as an important substrate for several redox reactions necessary to produce adenosine triphosphate (ATP). NAD+ also serves as an essential electron carrier, shifting between oxidized NAD+ to its reduced form NADH to modulate oxidative stress. NAD+ also serves as an important substrate for poly-ADP-ribose polymerases (PARPs), CD38/157 ectoenzymes, and histone deacetylases known as sirtuins, which are associated with DNA repair, apoptosis, calcium signaling and transcriptional regulation. These processes are fundamental for maintaining and promoting tumor growth and survival. Overexpression of several enzymes in the NAD+ biosynthesis pathway has been reported in several tumor types. There is increasing evidence of the impact of the overexpression of the de novo kynurenine pathway (KP) and several NAD+ salvage pathway enzymes, including nicotinamide phosphoribosyltransferase (NAMPT), nicotinic acid phosphoribosyltransferase (NAPRT), and nicotinamide N-methyltransferase (NNMT) on several tumorigenic processes including DNA repair, transcriptional regulation, secondary messenger and calcium signaling, cell proliferation, metastasization and angiogenesis, invasion, immunosurveillance, and drug resistance. Collectively, targeting NAD+ biosynthesis has emerged as a promising therapeutic strategy to lower NAD+ levels and impair cellular processes implicated in cancer biology for cancer treatment.
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Helman, T., Braidy, N. (2023). NAD+ as a Target for Cancer Treatment. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_269-1
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