STAT3 is a biologically relevant therapeutic target in H3K27M-mutant diffuse midline glioma.

ABSTRACT:

Background

H3K27M-mutant diffuse midline glioma (DMG) is a lethal brain tumor that usually occurs in children. Despite advances in our understanding of its underlying biology, efficacious therapies are severely lacking.

Methods

We screened a library of drugs either FDA-approved or in clinical trial using a library of patient-derived H3K27M-mutant DMG cell lines with cell viability as the outcome. Results were validated for clinical relevance and mechanistic importance using patient specimens from biopsy and autopsy, patient-derived cell lines, inhibition by gene knockdown and small molecule inhibitors, and patient-derived xenografts.

Results

Kinase inhibitors were highly toxic to H3K27M-mutant DMG cells. Within this class, STAT3 inhibitors demonstrated robust cytotoxi

SUBMITTER: Zhang L 

PROVIDER: S-EPMC9527528 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature