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Updated: Oct 3, 2025
Live-3D-Cell Immunocytochemistry Assays of Pediatric Diffuse Midline Glioma
Published on: November 11, 2021
[Diffuse midline glioma]
1Department of Neurosurgery, Nagoya University, Graduate School of Medicine.
Abstract:
Diffuse midline glioma(DMG), H3 K27M-mutant is an infiltrative midline high-grade glioma with predominantly astrocytic differentiation and a K27M mutation in either H3F3A or HIST1H3B/C. It is commonly located in the brain stem, thalamus, and spinal cord. DMG is predominant in children but can occur in adults. Brain stem disease, known as diffuse intrinsic pontine glioma(DIPG), is the representative: -80% harbor the H3 K27M mutation. Generally, the prognosis of DMG is poor: the 2-year survival rate is < 10%, despite intensive research and therapies. Consequently, radiation is the only treatment and there is no effective chemotherapeutic regimen. The recent findings concerning the genetic profiles of DMG shed light on precision medicine. Until today, approximately 250 clinical trials with molecular targeted therapy as a strategy have been conducted for different biological pathways in DMG. Unfortunately, none of them has shown significant efficacy for DMG. One of the problems in these clinical trials is insufficient knowledge of whether the used molecular targeted agents penetrate the blood-brain barrier. Continuous efforts to develop effective precision medicine against DMG should pave the way for overcoming DMG in the future.
Insights
Diffuse midline glioma (DMG), a K27M-mutant brain tumor, has a poor prognosis despite extensive research. Current treatments are limited, highlighting the need for effective precision medicine strategies targeting DMG.
Area of Science:
- Neuro-oncology
- Pediatric oncology
- Molecular pathology
Background:
- Diffuse midline glioma (DMG), H3 K27M-mutant, is an aggressive, infiltrative brain tumor predominantly affecting children.
- Commonly found in the brainstem (as diffuse intrinsic pontine glioma - DIPG), thalamus, and spinal cord, DMG has a dismal prognosis with a 2-year survival rate below 10%.
Purpose of the Study:
- To review the current understanding of diffuse midline glioma (DMG), H3 K27M-mutant.
- To highlight the challenges and future directions in developing effective precision medicine for DMG.
Main Methods:
- Review of scientific literature on DMG genetics, treatment, and clinical trials.
- Analysis of the efficacy of molecular targeted therapies and challenges in blood-brain barrier penetration.
Main Results:
- DMG is characterized by the H3 K27M mutation, present in ~80% of DIPG cases.
- Despite numerous clinical trials (~250) investigating molecular targeted therapies, none have demonstrated significant efficacy.
- A key challenge is the limited understanding of blood-brain barrier penetration for targeted agents.
Conclusions:
- Radiation therapy remains the primary treatment for DMG, with no effective chemotherapeutic options currently available.
- Further research into precision medicine, addressing challenges like drug delivery across the blood-brain barrier, is crucial for improving outcomes in DMG.
