BET protein inhibition sensitizes glioblastoma cells to temozolomide treatment by attenuating MGMT expression.

ABSTRACT: Bromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gen

SUBMITTER: Tancredi A 

PROVIDER: S-EPMC9747918 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature