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

Malignant cells depend on NAD metabolism, especially via NAMPT, to support proliferation, stress tolerance, and immune evasion, revealing a potential therapeutic vulnerability.

• Why it matters: NAD plays a central role in cellular functions like energy production, DNA repair, and signaling, and its metabolic rewiring in cancer offers opportunities for targeted therapies. Understanding this dependence is crucial for developing effective treatments.
• What they did: The authors review how NAD metabolism is altered in cancer, focusing on the roles of NAMPT, PARP enzymes, and NAD-consuming ectoenzymes, and discuss preclinical and clinical strategies targeting these pathways.
• The result: Targeting NAD biosynthesis and consumption shows promise in preclinical and some clinical settings, but barriers remain to fully exploiting NAD metabolism as a cancer therapy.