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Histone H3.3 Targeted Therapy for Pediatric High-grade Gliomas

University of California, Davis Medical Center
Paul Knoepfler, PhD
Grant Type: 
Innovation Grants
Year Awarded: 
Type of Childhood Cancer: 
Brain Tumors, Glioma, Medulloblastoma, Neuroblastoma
Project Description: 


High-grade pediatric gliomas are catastrophic cancers. Greater than 90% of children with these tumors die within two years of diagnosis even with today's best treatments, which are based on adult therapies and have devastating side effects. There is an urgent need for new, more effective therapies that are specifically designed for children because pediatric gliomas are different from adult.

Project Goal:

A potential novel treatment approach comes from the recent observation that the H3.3 and MYC genes are mutated specifically in these tumors making these factors innovative therapeutic targets. We propose to test the hypothesis that mutant H3.3 and MYC act together in a pathway to transform normal stem cells into glioma cancer cells, and that this newly discovered pediatric glioma pathway can be targeted for inhibition. We will make use of cutting edge genomics and gene editing technology to test our hypothesis. The proposed work will contribute to the mission of ALSF by providing a major advance in the understanding of the biology and causes of childhood brain cancer and by using that knowledge to catalyze and test potential new treatments that are safer and more effective. Our ultimate goal is a cure for childhood glioma via treatments that are more precise and molecularly targeted (versus systemic), less toxic, and have higher efficacy. The data will also provide key insights into a broader range of pediatric tumors driven by MYC as well including medulloblastoma and neuroblastoma. Thus, transformative advances in the therapy of pediatric gliomas and other childhood tumors are expected.