The role of extracellular and intracellular Nicotinamide phosphoribosyl-transferase in cancer: Diagnostic and therapeutic perspectives and challenges.

Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties. Nampt is upregulated in many malignancies, including obesity-associated cancers, and is associated with worse prognosis. Serum Nampt may be a potential diagnostic and prognostic biomarker in cancer. Pharmacologic agents that neutralize Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer treatments. In particular, Nampt inhibitors as monotherapy or in combination therapy have displayed anti-cancer activity in vivo and in vitro. The aim of this review is to explore the role of Nampt in cancer pathophysiology as well as to synopsize the mechanisms underlying the association between extracellular and intracellular Nampt, and malignancy. Exploring the interplay of cellular bioenergetics, inflammation and adiposopathy is expected to be of importance in the development of preventive and therapeutic strategies against cancer.