Combination drug screen targeting glioblastoma core vulnerabilities reveals pharmacological synergisms.

ABSTRACT:

Background

Pharmacological synergisms are an attractive anticancer strategy. However, with more than 5000 approved-drugs and compounds in clinical development, identifying synergistic treatments represents a major challenge.

Methods

High-throughput screening was combined with target deconvolution and functional genomics to reveal targetable vulnerabilities in glioblastoma. The role of the top gene hit was investigated by RNA interference, transcriptomics and immunohistochemistry in glioblastoma patient samples. Drug combination screen using a custom-made library of 88 compounds in association with six inhibitors of the identified glioblastoma vulnerabilities was performed to unveil pharmacological synergisms. Glioblastoma 3D spheroid, organotypic ex vivo and syngeneic orthot

SUBMITTER: Ariey-Bonnet J 

PROVIDER: S-EPMC10433015 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature