Optimal therapeutic targeting by HDAC inhibition in biopsy-derived treatment-naive diffuse midline glioma models.

ABSTRACT:

Background

Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine gliomas (DIPGs), have a dismal prognosis, with less than 2% surviving 5 years postdiagnosis. The majority of DIPGs and all DMGs harbor mutations altering the epigenetic regulatory histone tail (H3 K27M). Investigations addressing DMG epigenetics have identified a few promising drugs, including the HDAC inhibitor (HDACi) panobinostat. Here, we use clinically relevant DMG models to identify and validate other effective HDACi and their biomarkers of response.

Methods

HDAC inhibitors were tested across biopsy-derived treatment-naïve in vitro and in vivo DMG models with biologically relevant radiation resistance. RNA sequencing was performed to define and compare drug efficacy and to map predictive bio

SUBMITTER: Vitanza NA 

PROVIDER: S-EPMC7992886 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature