Targeting PDGFRα-activated glioblastoma through specific inhibition of SHP-2-mediated signaling.

ABSTRACT:

Background

Glioblastoma (GBM) is the most malignant primary brain tumor, with dismal median survival. Treatment of GBM is particularly challenging given the intrinsic resistance to chemotherapy and difficulty of drugs to reach the tumor beds due to the blood-brain barrier. Here, we examined the efficacy of SHP099, a potent, selective, and oral SHP-2 inhibitor for treating GBM with activated platelet derived growth factor receptor alpha (PDGFRα) signaling.

Methods

The effects of SHP099 on cell survival of neural progenitor cells (NPCs), GBM cell lines, and patient-derived glioma stem-like cells (GSCs) were evaluated. Brain and plasma pharmacokinetics of SHP099 and its ability to inhibit SHP-2 signaling were assessed. SHP099 efficacy as a single agent or in combination with te

SUBMITTER: Sang Y 

PROVIDER: S-EPMC6827835 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature