Targeting Master Regulator Dependencies in Diffuse Intrinsic Pontine Glioma (DIPG)

Diffuse intrinsic pontine glioma (DIPG) remains a fatal disease and the identification and development of new treatment approaches are greatly needed. A novel computational-experimental Cancer Systems Biology approach involves identifying the interactions of master regulator (MR) proteins, with mutations and their influence on cancer development. This approach may also predict and prioritize drugs that reverse the effects of these interactions. This study will apply such an approach to evaluate new treatment strategies for patients with DIPG. Researchers will analyze the Pediatric Brain Tumor Atlas and other DIPG gene expression data using innovative computational methods. This analysis will describe the interactions of MR proteins in DIPG tumors and prioritize drugs by their ability to shut down the most aberrant MR proteins. This method can be targeted to individual patient samples and across the disease as a whole allowing for subtyping of tumors to occur while characterizing DIPG gene regulatory networks overall. This project will evaluate the efficacy of treatments predicted by the MR approach in patient-derived DIPG cell lines and animal models. This will advance drug development and suggest novel therapy approaches in DIPG to improve outcomes in this difficult-to-treat disease.