A context-dependent framework for targeting NAD metabolism in cancer.

This paper highlights the potential of targeting NAD metabolism in cancer treatment, though specific findings are not provided.

Summary and findings

This study reviews the role of NAD metabolism in cancer, focusing on its impact on cellular homeostasis and the potential for therapeutic targeting. It discusses the mechanisms by which cancer cells adapt their NAD production and the implications for treatment strategies. No specific numeric findings or experimental results are reported in the abstract.

Abstract

Nicotinamide adenine dinucleotide (NAD) occupies a privileged position at the intersection of cellular bioenergetics, redox homeostasis, and signal transduction. Beyond its canonical role in ATP synthesis, NAD serves as an obligate cofactor for enzymes including poly(ADP-ribose) polymerases (PARPs), sirtuins, and CD38, thereby regulating DNA repair, epigenetic remodeling, and inflammatory signaling. Thus, NAD metabolism supports the preservation of cellular homeostasis against oncogenic insults. Malignant transformation, however, imposes substantial biosynthetic and genotoxic stress, often driving metabolic adaptations that amplify NAD production via nicotinamide phosphoribosyltransferase (NAMPT). This endows cancer cells with enhanced proliferative capacity, stress tolerance, and immunoevasive features. Importantly, the dependence of malignant cells on sustained NAD availability constitutes a therapeutically exploitable vulnerability. Accordingly, NAMPT inhibitors, PARP inhibitors, and strategies targeting NAD-consuming ectoenzymes have shown preclinical and, in select settings, clinical efficacy. Here, we critically review the rewiring of NAD metabolism in cancer, associated therapeutic opportunities, and barriers to their clinical exploitation.

Limitations

Not reported in abstract.

Elsewhere in the NAD+ (Nicotinamide Adenine Dinucleotide) corpus