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.