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Roulston A, Shore GC. New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology. Mol Cell Oncol. 2015;3(1):e1052180doi: 10.1080/23723556.2015.1052180.
Roulston, A., & Shore, G. C. (2016). New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology. Molecular & cellular oncology, 3(1), e1052180. https://doi.org/10.1080/23723556.2015.1052180
Roulston, Anne, and Shore, Gordon C. "New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology." Molecular & cellular oncology vol. 3,1 (2016): e1052180. doi: https://doi.org/10.1080/23723556.2015.1052180
Roulston A, Shore GC. New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology. Mol Cell Oncol. 2015 Jun 10;3(1):e1052180. doi: 10.1080/23723556.2015.1052180. eCollection 2016 Jan. PMID: 27308565; PMCID: PMC4845202.
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Mol Cell Oncol. 2015 Jun 10;3(1):e1052180. doi: 10.1080/23723556.2015.1052180. eCollection 2016 Jan.

New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology.

Molecular & cellular oncology

Anne Roulston, Gordon C Shore

Affiliations

  1. Laboratory for Therapeutic Development, Rosalind and Morris Goodman Cancer Research Centre, and Dept. Biochemistry, McGill University , Montreal, QC, Canada.

PMID: 27308565 PMCID: PMC4845202 DOI: 10.1080/23723556.2015.1052180

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 inhibitors did not achieve single-agent therapeutic levels before dose-limiting toxicities were reached, a new understanding of alternative rescue pathways and a biomarker that can be used to select patients provides new opportunities to widen the therapeutic window and achieve efficacious doses in the clinic. Recent work has also illustrated the potential for drug combination strategies to further enhance the therapeutic opportunities. This review summarizes recent discoveries in NAD(+)/NAMPT inhibitor biology in the context of exploiting this new knowledge to optimize the clinical outcomes for this promising new class of agents.

Keywords: DNA damage; NAMPT; NAPRT1; PARP; niacin

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