CDKN2A/B Homozygous Deletion Sensitizes IDH-Mutant Glioma to CDK4/6 Inhibition.

ABSTRACT:

Purpose

Treatment paradigms for isocitrate dehydrogenase (IDH)-mutant gliomas are rapidly evolving. Although typically indolent and responsive to initial treatment, these tumors invariably recur at a higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcomes. We investigated the effect of CDK-Rb pathway blockade on IDH-mutant glioma growth in vitro and in vivo using CDK4/6 inhibitors (CDKi).

Experimental design

Cell viability, proliferation assays, and flow cytometry were used to examine the pharmacologic effect of two distinct CDKi, palbociclib and abemaciclib, in multiple patient-derived IDH-mutant glioma lines. Isogenic models were used to directly in

SUBMITTER: Nasser AM 

PROVIDER: S-EPMC11250907 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature