2015
DOI: 10.1080/23723556.2015.1052180
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New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology

Abstract: Nicotinamide phosphoribosyltransferase (NAMPT) is crucial for nicotinamide adenine dinucleotide (NAD+) biosynthesis in mammalian cells. NAMPT inhibitors represent multifunctional anticancer agents that act on NAD+ metabolism to shut down glycolysis, nucleotide biosynthesis, and ATP generation and act indirectly as PARP and sirtuin inhibitors. The selectivity of NAMPT inhibitors preys on the increased metabolic requirements to replenish NAD+ in cancer cells. Although initial clinical studies with NAMPT inhibito… Show more

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Cited by 39 publications
(44 citation statements)
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“…In support of this, it has been demonstrated that clinically available chemical inhibitors of NAD + biosynthesis enhances the cell killing effect of DNA damaging agents when BER is defective or inhibited [70]. More recently, inhibitors of NAD + biosynthesis have been suggested to be considered for cancer treatment modalities in general [71]. …”
Section: Relationship Between Base Excision Repair and Metabolismmentioning
confidence: 99%
“…In support of this, it has been demonstrated that clinically available chemical inhibitors of NAD + biosynthesis enhances the cell killing effect of DNA damaging agents when BER is defective or inhibited [70]. More recently, inhibitors of NAD + biosynthesis have been suggested to be considered for cancer treatment modalities in general [71]. …”
Section: Relationship Between Base Excision Repair and Metabolismmentioning
confidence: 99%
“…NAMPT inhibitors as single agents have not been applied successfully in clinical studies so far [6]. Possible successful treatment combinations with NAMPT inhibitors include DNA-damaging agents, inhibitors targeting enzymes involved in cellular stress responses or DNA repair, and rescue with nicotinic acid in nicotinic acid phosphoribosyltransferase-negative tumors to increase tolerance of non-tumor tissue to NAMPT inhibition [6]. Another promising possibility is the simultaneous inhibition of NAMPT and other enzymes providing precursors for NAD biosynthesis, e.g.…”
Section: Inhibition Of Nad Biosynthesis In Hccmentioning
confidence: 99%
“…Cancer cells have a higher demand for NAD because of their rapid proliferation which is associated with the need for increased energy metabolism, ATP generation, nucleotide biosynthesis, DNA repair, and increased activity of NADconsuming enzymes [6]. NAMPT has been extensively studied as a target of anticancer therapy.…”
Section: Inhibition Of Nad Biosynthesis In Hccmentioning
confidence: 99%
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