Identification of novel biologic targets in the treatment of newly diagnosed diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine gliomas (DIPGs) carry an extremely poor prognosis. Standard practice has been to base the diagnosis on classic imaging and clinical characteristics and to treat with focal radiation therapy, usually accompanied with experimental therapy. As a result of the desire to avoid upfront biopsy, little has been learned regarding the molecular features of this disease. Findings from several autopsy series have included loss of p53 and PTEN, and amplification of PDGFR. Based on these and other findings, murine models have been generated and provide a new tool for preclinical testing. DIPG biopsy at diagnosis has increasingly become incorporated into national protocols at several centers, bringing the prospect of a better understanding of DIPG biology in the future. Initial analyses of pretreatment tumors cast valuable new light and establish the importance of p53 inactivation and the RTK-PI3K pathway in this disease.