A large-scale drug screen identifies selective inhibitors of class I HDACs as a potential therapeutic option for SHH medulloblastoma
Ontology highlight
ABSTRACT: Here we performed a targeted small molecule screen on a stable, SHH-dependent murine MB cell line (SMB21). A subset of the HDAC inhibitors tested significantly inhibit tumor growth of SMB21 cells by preventing SHH pathway activation. Of note, class I HDAC inhibitors were also efficacious in suppressing growth of diverse SMO inhibitor-resistant clones of SMB21 cells. Finally, we show that the novel HDAC inhibitor Quisinostat (JNJ) targets multiple class I HDACs, is well tolerated in mouse models and robustly inhibits growth of SHH MB cells in vivo as well as in vitro. Our data provide strong evidence that Quisinostat (JNJ) or other class I HDAC inhibitors might be therapeutically useful for patients with SHH MB including those resistant to SMO inhibition.
ORGANISM(S): Mus musculus
PROVIDER: GSE129512 | GEO | 2019/04/10
REPOSITORIES: GEO
ACCESS DATA