New Investigator Grant Awarded to Zach Reitman

DIPGs are incurable pediatric brain tumors for which new therapies are urgently needed. The only effective treatment is radiation therapy, but the tumor inevitably progresses after treatment and almost always leads to death within 18 months. Inhibition of the DNA damage sensing kinase ATM selectively increases the efficacy of radiation therapy in tumors that have mutations in genes that regulate the DNA damage response. Since DIPGs frequently contain mutations in key components of the DNA damage response pathway, an intriguing open question is whether DIPGs might be susceptible to radiosensitization by ATM inhibition. The proposed work will test whether this is the case in faithful genetically-engineered mouse models of the most frequent genetic subtypes of DIPG. We will determine the molecular mechanism by which specific genetic subtypes of DIPG can be radiosensitized in this manner. These results will identify which children with DIPG should be enrolled on clinical trials of ATM inhibitors combined with radiation therapy.