Diffuse Intrinsic Pontine Glioma: New Pathophysiological Insights and Emerging Therapeutic Targets

ABSTRACT: BACKGROUND: Diffuse Intrinsic Pontine Glioma (DIPG) is the leading cause of brain tumor-related death in children, with median survival of less than one year. Despite decades of clinical trials, there has been no improvement in prognosis since the introduction of radiotherapy over thirty years ago. OBJECTIVE: To review the clinical features and current treatment challenges of DIPG, and discuss emerging insights into the unique genomic and epigenomic mechanisms driving DIPG pathogenesis that present new opportunities for the identification of therapeutic targets. CONCLUSION: In recent years, an increased availability of biopsy and rapid autopsy tissue samples for preclinical investigation has combined with the advent of new genomic and epigenomic profiling tools to yield remarkable advancements in our understanding of DIPG disease mechanisms. As well, a deeper understanding of the developmental context of DIPG is shedding light on therapeutic targets in the microenvironment of the childhood brain.