Beyond cell cycle control: CDKN2A loss is associated with altered NAD+ metabolic states and increased sensitivity to NAMPT inhibition in glioblastoma.

Abstract

While CDKN2A loss is classically associated with cell cycle deregulation through the p16-Cdk4-Rb axis, our findings suggest an additional layer of metabolic vulnerability arising from altered NAD⁺ homeostasis in CDKN2A-deleted glioblastoma, revealing a metabolic-genetic interface for rationally revisiting NAD⁺ targeting strategies, moving beyond the broad inhibition approaches.