Diffuse intrinsic pontine glioma: Insights into oncogenesis and opportunities for targeted therapy

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a lethal brainstem tumor that most commonly occurs in young children between the ages of five and ten. DIPG is the leading cause of brain tumor-related death in childhood, with most patients succumbing to the disease within two years of diagnosis. Attempts to improve survival through clinical trials have been futile thus far, with standard of care remaining focal radiation which provides only modest benefit. While tumor tissue is not considered necessary for diagnosis and management unless there are atypical features, the development of stereotactic biopsy through neurosurgical technical advancements and the brave donations of patients and their families has allowed for a vast increase in our understanding of DIPG tumorigenesis. This practice also allowed for the development of in-vitro and in-vivo models which have proven instrumental for testing pre-clinical hypotheses and designing the next generation of biologically-informed clinical trials. In this review, we will detail the epigenetic and molecular drivers of DIPG, as well as the current outlook for targeted therapies.

Keywords

• DIPG
• Diffuse intrinsic pontine glioma
• Epigenetics
• Targeted therapy