Modulating native GABA_A receptors in medulloblastoma with positive allosteric benzodiazepine-derivatives induces cell death.

ABSTRACT:

Purpose

Pediatric brain cancer medulloblastoma (MB) standard-of-care results in numerous comorbidities. MB is comprised of distinct molecular subgroups. Group 3 molecular subgroup patients have the highest relapse rates and after standard-of-care have a 20% survival. Group 3 tumors have high expression of GABRA5, which codes for the α5 subunit of the γ-aminobutyric acid type A receptor (GABA_AR). We are advancing a therapeutic approach for group 3 based on GABA_AR modulation using benzodiazepine-derivatives.

Methods

We performed analysis of GABR and MYC expression in MB tumors and used molecular, cell biological, and whole-cell electrophysiology approaches to establish presence of a functional 'druggable' GABA_AR in group 3 cells.

Results

SUBMITTER: Kallay L 

PROVIDER: S-EPMC6478651 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature