Exploiting NAD Metabolism Defects in Pediatric Brain Tumors

Dr. Ranjit Bindra – Yale University, New Haven, CT

Better therapies are needed for pediatric brain tumors, especially those which target the underlying mutations associated with these cancers. We discovered that mutations in a gene, PPM1D, which are commonly seen across multiple unique types of pediatric brain tumors, induce profound defects in cellular metabolism. These defects induce exquisite sensitivity to a class of drugs which target this metabolic pathway, which have been tested before in clinical trials for other tumors. Here, we seek to develop a novel regimen using these drugs against pediatric brain tumors with PPM1D mutations. We will test our approach using pediatric brain tumor models in vitro and in vivo. The work proposed in this application will form the basis for advancing these drugs into clinical trials, and thus has the potential to uncover new therapeutics for children with brain tumors.