IPRD funded research by Akash Gunjan
Pediatric high-grade glioma: Histones are small, positively charged nuclear proteins that bind DNA and package it into chromosomes, thereby regulating all DNA-associated functions. Mutations in histone variant H3.3 drive pediatric high-grade gliomas such as diffuse intrinsic pontine glioma (DIPG; ~300 cases annually in the US). DIPG tumors are localized in the brain stem and cannot be surgically excised. These tumors are 100% fatal and there is a desperate need for therapies. We have identified at least four aberrant epigenetic and DNA repair pathways in H3.3 mutant DIPG cells that drive these cancers, and can be targeted using repurposed Food and Drug Administration (FDA) approved drugs, although the ability of some of these drugs to cross the Blood Brain Barrier (BBB) is unclear. This research project will test combinations of radiation with four classes of FDA approved drugs to find the best combination for eliminating DIPG tumors while sparing normal cells.
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