Abstract
Pediatric diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis that has not seen a change in outcome despite multiple clinical trials. Possible reasons for failure to make progress in this aggressive childhood brain tumor include: poor understanding of the underlying molecular biology due to lack of access to tumor material; absence of accurate and relevant DIPG preclinical models for drug development; ill-defined therapeutic targets for novel agents; and inadequate drug delivery to the brainstem. This review will demonstrate that systematic studies to identify solutions for each of these barriers is starting to deliver progress that can turn pessimism to optimism in DIPG.