PTEN deficiency leads to proteasome addiction: a novel vulnerability in glioblastoma.

ABSTRACT:

Background

Glioblastoma (GBM) is the most common primary brain tumor in adults with a median survival of approximately 15 months; therefore, more effective treatment options for GBM are required. To identify new drugs targeting GBMs, we performed a high-throughput drug screen using patient-derived neurospheres cultured to preferentially retain their glioblastoma stem cell (GSC) phenotype.

Methods

High-throughput drug screening was performed on GSCs followed by a dose-response assay of the 5 identified original "hits." A PI3K/mTOR dependency to a proteasome inhibitor (carfilzomib), was confirmed by genetic and pharmacologic experiments. Proteasome Inhibition Response Signatures were derived from proteomic and bioinformatic analysis. Molecular mechanism of action was determine

SUBMITTER: Benitez JA 

PROVIDER: S-EPMC8661409 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature