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

A novel cancer systems biology approach identifies master regulator (MR) proteins that are necessary for tumor growth and predicts and prioritizes drugs that reverse their effects. This study will apply such an approach to identify much-needed new treatment strategies in DIPG, a universally fatal disease. We will analyze the PBTA-CBTTC and other DIPG gene expression data using innovative computational algorithms to: 1) describe the landscape of MR proteins in DIPG tumors, 2) prioritize drugs by their ability to shut down the most aberrant MR proteins both in individual patient samples and across the disease as a whole, and 3) evaluate the efficacy of treatments predicted by the MR approach in patient-derived DIPG cell lines and animal models.