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.