New Investigator Grant Awarded to Zach Reitman

DIPGs are incurable pediatric brain tumors for which new treatment strategies are urgently needed. The only known effective treatment is radiation therapy, but DIPGs eventually return after this treatment and almost always lead to death within 18 months. A promising new potential treatment approach for DIPG is to combine radiation therapy with targeted treatments against a molecule in the tumors called ATM. This approach has shown promise in the laboratory. This finding raises the hope that drugs that inhibit ATM could be given to children with DIPG as they undergo radiation therapy to increase the effectiveness of the radiation treatments. However, based on our experiments some subtypes of DIPG appear to be resistant to the combination of radiation therapy and targeting ATM. Here we will carry out experiments to determine why some DIPGs may be resistant to this combination treatment approach. This work will be done in genetically faithful primary mouse models of DIPG. These results will provide mechanistic information on the biology of DIPG and how ATM inhibitors may work in DIPG. The results will also help identify which children with DIPG should be enrolled on future clinical trials of ATM inhibitors combined with radiation therapy. Furthermore the results will help select combinations of treatments that could be used to overcome resistance in future studies.