The third-generation EGFR inhibitor AZD9291 overcomes primary resistance by continuously blocking ERK signaling in glioblastoma.

ABSTRACT:

Background

Glioblastoma (GBM) is a fatal brain tumor, lacking effective treatment. Epidermal growth factor receptor (EGFR) is recognized as an attractive target for GBM treatment. However, GBMs have very poor responses to the first- and second-generation EGFR inhibitors. The third-generation EGFR-targeted drug, AZD9291, is a novel and irreversible inhibitor. It is noteworthy that AZD9291 shows excellent blood-brain barrier penetration and has potential for the treatment of brain tumors.

Methods

In this study, we evaluated the anti-tumor activity and effectiveness of AZD9291 in a preclinical GBM model.

Results

AZD9291 showed dose-responsive growth inhibitory activity against six GBM cell lines. Importantly, AZD9291 inhibited GBM cell proliferation > 10 times more effic

SUBMITTER: Liu X 

PROVIDER: S-EPMC6533774 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature