Treatment strategies in diffuse midline gliomas with the H3K27M mutation: The role of convection-enhanced delivery in overcoming anatomic challenges

Benjamin T. Himes, Liang Zhang, David J. Daniels

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations

Abstract

Diffuse midline gliomas harboring the H3 K27M mutation-including the previously named diffuse intrinsic pontine glioma (DIPG)-are lethal high-grade pediatric brain tumors that are inoperable and without cure. Despite numerous clinical trials, the prognosis remains poor, with a median survival of ~1 year from diagnosis. Systemic administration of chemotherapeutic agents is often hindered by the blood brain barrier (BBB), and even drugs that successfully cross the barrier may suffer from unpredictable distributions. The challenge in treating this deadly disease relies on effective delivery of a therapeutic agent to the bulk tumor as well as infiltrating cells. Therefore, methods that can enhance drug delivery to the brain are of great interest. Convection-enhanced delivery (CED) is a strategy that bypasses the BBB entirely and enhances drug distribution by applying hydraulic pressure to deliver agents directly and evenly into a target region. This technique reliably distributes infusate homogenously through the interstitial space of the target region and achieves high local drug concentrations in the brain. Moreover, recent studies have also shown that continuous delivery of drug over an extended period of time is safe, feasible, and more efficacious than standard single session CED. Therefore, CED represents a promising technique for treating midline tumors with the H3K27M mutation.

Original languageEnglish (US)
Article number31
JournalFrontiers in Oncology
Volume9
Issue numberFEB
DOIs
StatePublished - 2019

Keywords

  • Alternative delivery method
  • Blood brain barrier (BBB)
  • Convection-enhanced delivery (CED)
  • Diffuse intrinsic pontine glioma (DIPG)
  • H3K27M mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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