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Beyond Cell Cycle Control: CDKN2A Loss Orchestrates NAD⁺ Metabolic Plasticity and NAMPT Inhibitor Sensitivity in Glioblastoma

Dubey, S.; Yu, G.; Aboul-Hosn, R.; Tse, C.; Nathanson, D. A.; Lai, A.; Vossel, K.; Rodriguez, F. J.

2025-12-04 cancer biology
10.64898/2025.12.02.691903 bioRxiv
Show 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 previously unrecognized metabolic-genetic interface for rationally revisiting NAD+ targeting strategies, moving beyond the broad inhibition approaches.

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