BRD9 inhibition overcomes oncolytic virus therapy resistance in glioblastoma.

ABSTRACT: Long-term survival of glioblastoma multiforme (GBM) remains challenging, spurring the development of novel therapies such as oncolytic virus therapy. While oncolytic virus shows promise in clinical trials, many patients do not respond to this therapy. Here, we perform a CRISPR screening and identify the non-canonical BRG1/BRM-associated factor (ncBAF) complex as a pivotal tumor-intrinsic factor for oncolytic virotherapy resistance. Knocking out the ncBAF-specific subunit bromodomain-containing protein 9 (BRD9) markedly augments the oncolytic efficacy of oncolytic herpes simplex virus type 1 (oHSV1) and enhances antitumor immunity. Mechanistically, BRD9 binds to RELA and potentiates the expression of downstream antiviral genes. Notably, the application of BRD9 inhibitor (IBRD9) significantl

SUBMITTER: Guo C 

PROVIDER: S-EPMC12432354 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature