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bioRxivCancer BiologyPreprint

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

Swati DubeyiD, Guanqiao Yu, Ryana Aboul-Hosn, Christopher Tse, David A. NathansoniD, Albert LaiiD, Keith A. VosseliD, Fausto J. RodrígueziD

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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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