DIPG-06. Uncovering the FACTs in Diffuse Midline Glioma (DMG)

ABSTRACT: Abstract Effective treatments are urgently needed for the incurable paediatric brainstem tumour Diffuse Midline Glioma (DMG). Most DMGs contain Histone H3 mutations (H3K27M), which produce extensive epigenetic dysregulation by inhibiting EZH2-mediated trimethylation of H3K27 (H3K27me3). Global depletion of the repressive H3K27me3 modification results in aberrantly open chromatin and is central to DMG tumorigenesis. Thus, targeting the epigenome is a promising avenue of treatment for DMG. We found that targeting the histone chaperone complex Facilitates Chromatin Transcription (FACT) with the curaxin drug CBL0137 to have potent pre-clinical efficacy against DMG, leading to a paediatric Phase I/II clinical trial for CBL0137 which includes a DMG/DIPG cohort (NCT04870944). In this project we a

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PROVIDER: S-EPMC9165134 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature