Regulation of cancer and cancer-related genes via NAD ⁺

Significance: NAD ⁺ is an essential redox cofactor in cellular metabolism and has emerged as an important regulator of a wide spectrum of disease conditions, most notably, cancers. As such, various strategies targeting NAD ⁺ synthesis in cancers are in clinical trials. Recent Advances: Being a substrate required for the activity of various enzyme families, especially sirtuins and poly(adenosine diphosphate [ADP]-ribose) polymerases, NAD ⁺ -mediated signaling plays an important role in gene expression, calcium release, cell cycle progression, DNA repair, and cell proliferation. Many strategies exploring the potential of interfering with NAD ⁺ metabolism to sensitize cancer cells to achieve anticancer benefits are highly promising, and are being pursued. Critical Issues: With the multifaceted roles of NAD ⁺ in cancer, it is important to understand how cellular processes are reliant on NAD ⁺ . This review summarizes how NAD ⁺ metabolism regulates various pathophysiological processes in cancer, and how this knowledge can be exploited to devise effective anticancer therapies in clinical settings. Future Directions: In line with the redundant pathways that facilitate NAD ⁺ metabolism, further studies should comprehensively understand the roles of the various NAD ⁺ -synthesizing as well as NAD ⁺ -utilizing biomolecules to understand its true potential in cancer treatment.