Targeting Transcriptional Elongation in Pediatric Glioma

The goal of project is to test the hypothesis that inhibition of Pol II transcriptional elongation in combination with BRD4 inhibition will further suppress gene transcription and will either delay or prevent DIPG from acquiring resistance to monotherapy. This dual inhibition approach will interfere with gene transcription at two levels: transcriptional initiation (BRD4) and elongation (Pol II). This project will also explore how these targeted therapies interact with radiation in treating DIPG, which is important due to the use of radiation in treating nearly all cases of DIPG in children. The successful completion of proposal study has significant impact on clinical practice and accumulating data from this research could therefore lay the foundation for early clinical trials of this approach, given the high unmet need and orphan disease status of DIPG.