Diffuse intrinsic pontine gliomas: translation of genomic knowledge to clinical practice

Tina Zhou, Sara Khan, Ron Firestein, Peter Downie, Jason Cain

Research output: Contribution to journalReview ArticleResearch


Pediatric brain tumors account for approximately 25% of all cancers in children and are currently the leading cause of cancer-related deaths in the pediatric population with an estimated incidence of 5.14 cases per 100,000 person years [1]. Up to 10-15% of all pediatric brain tumors arise in the brainstem, with the majority of these classified as the diffuse intrinsic pontine glioma (DIPG) subtype [2]. The outcome of children with DIPG remains dismal with a median survival of <1 year. Owing to the unique location of DIPGs, surgical intervention is unachievable due to difficulty of physical access and the diffuse infiltration of the tumor throughout the pons. Radiotherapy has thus far been the only method identified to provide transient benefit in the setting of a uniformly fatal outcome. Decades of laboratory studies and clinical trials have failed to identify any chemotherapies delivering survival benefit, either alone or as an adjunct to radiotherapy. Advances in surgical biopsy techniques and next generation sequencing modalities have more recently provided a better understanding of the distinct pathophysiology of DIPGs and opened new windows of opportunity for the development of molecular-targeted therapies with hope of delivering more effective treatment for children suffering from DIPG whilst minimizing systemic toxicity. In this review, we will explore the recent advances in the genomic understanding and treatment of DIPG, and the resulting outcomes of the preclinical and clinical drug trials which are guiding the next wave of therapeutic discovery for this disease of unmet clinical need.
Original languageEnglish
Article number022
Number of pages26
JournalOBM Neurobiology
Issue number1
Publication statusPublished - Mar 2019


  • Diffuse intrinsic pontine glioma
  • genetics
  • Histone H3
  • Epigenetic
  • targeted therapy
  • Clinical trials

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