ATM inhibition enhances the efficacy of radiation across distinct molecular subgroups of pediatric high-grade glioma.

ABSTRACT:

Background

Pediatric high-grade glioma (pHGG) is largely incurable and accounts for most brain tumor-related deaths in children. Radiation is a standard therapy, yet the benefit from this treatment modality is transient, and most children succumb to disease within 2 years. Recent large-scale genomic studies suggest that pHGG has alterations in DNA damage response (DDR) pathways that induce resistance to DNA damaging agents. The aim of this study was to evaluate the therapeutic potential and molecular consequences of combining radiation with selective DDR inhibition in pHGG.

Methods

We conducted an unbiased screen in pHGG cells that combined radiation with clinical candidates targeting the DDR and identified the ATM inhibitor AZD1390. Subsequently, we profiled AZD1390 + radia

SUBMITTER: Xie J 

PROVIDER: S-EPMC10547515 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature