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Review
. 2019 Jul 10;21(8):37.
doi: 10.1007/s11940-019-0577-y.

Diffuse Intrinsic Pontine Glioma: From Diagnosis to Next-Generation Clinical Trials

Nicholas A Vitanza  1   2   3 , Michelle Monje  4
Affiliations
Review

Diffuse Intrinsic Pontine Glioma: From Diagnosis to Next-Generation Clinical Trials

Nicholas A Vitanza et al. Curr Treat Options Neurol. .

Abstract

Purpose of review: This review of diffuse intrinsic pontine glioma (DIPG) provides clinical background, a systematic approach to diagnosis and initial care, and synthesizes historical, modern, and future directions for treatment. We present evidence supporting neurosurgical biopsy, early palliative care involvement, limitation of glucocorticoid use, and the leveraging of preclinical DIPG models as a pipeline to next-generation clinical trials.

Recent findings: New molecular understanding of pediatric high-grade gliomas has led to the reclassification of DIPG as one member of a family of diffuse gliomas occurring in the midline of the central nervous system that exhibit pathognomonic mutations in genes encoding histone 3 (H3 K27M). DIPG remains a clinically relevant term, though diagnostically the 80% of DIPG cases that exhibit the H3 K27M mutation have been reclassified as diffuse midline glioma, H3 K27M-mutant. Re-irradiation has been shown to be well-tolerated and of potential benefit. Epigenetic targeting of transcriptional dependencies in preclinical models is fueling molecularly targeted clinical trials. Chimeric antigen receptor T cell immunotherapy has also demonstrated efficacy in preclinical models and provides a promising new clinical strategy. DIPG is a universally fatal, epigenetically driven tumor of the pons that is considered part of a broader class of diffuse midline gliomas sharing H3 K27M mutations. Radiation remains the standard of care, single-agent temozolomide is not recommended, and glucocorticoids should be used only sparingly. A rapid evolution of understanding in the chromatin, signaling, and immunological biology of DIPG may soon result in clinical breakthroughs.

Keywords: DIPG; DMG; Diffuse intrinsic pontine glioma; Diffuse midline glioma; H3 K27M mutation.

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Conflict of interest statement

Conflict of Interest

Nicholas A. Vitanza declares no potential conflicts of interest. Michelle Monje has a pending patent entitled “CAR T cell therapy to treat H3K27M midline gliomas.”

Figures

Fig. 1.
Fig. 1.
MRI images of a radiographically classic DIPG, including a axial T2 FLAIR and b sagittal T1 post-contrast images. Diffuse enlargement of the ventral pons and encasement of the basilar artery are classic signs.
See this image and copyright information in PMC

References

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      Wu et al., Khuong-Quang et al. and Schwartzentruber et al. discovered the highly recurrent H3 K27M mutation in DIPG and other pediatric midline gliomas. This discovery of an “oncohistone” has revolutionized our understanding of the pathophysiology of this disease and underscores the central role for epigenetic dysregulation in DIPG and other pediatric malignancies.