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Bioengineering 2018, 5(4), 88; https://doi.org/10.3390/bioengineering5040088

Cutting Edge Therapeutic Insights Derived from Molecular Biology of Pediatric High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)

1
Department of Pediatrics—Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2
The University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA
3
Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
4
Department of Pediatrics—Patient Care, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Received: 8 August 2018 / Revised: 12 October 2018 / Accepted: 15 October 2018 / Published: 18 October 2018
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
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Abstract

Pediatric high-grade glioma (pHGG) and brainstem gliomas are some of the most challenging cancers to treat in children, with no effective therapies and 5-year survival at ~2% for diffuse intrinsic pontine glioma (DIPG) patients. The standard of care for pHGG as a whole remains surgery and radiation combined with chemotherapy, while radiation alone is standard treatment for DIPG. Unfortunately, these therapies lack specificity for malignant glioma cells and have few to no reliable biomarkers of efficacy. Recent discoveries have revealed that epigenetic disruption by highly conserved mutations in DNA-packaging histone proteins in pHGG, especially DIPG, contribute to the aggressive nature of these cancers. In this review we pose unanswered questions and address unexplored mechanisms in pre-clinical models and clinical trial data from pHGG patients. Particular focus will be paid towards therapeutics targeting chromatin modifiers and other epigenetic vulnerabilities that can be exploited for pHGG therapy. Further delineation of rational therapeutic combinations has strong potential to drive development of safe and efficacious treatments for pHGG patients. View Full-Text
Keywords: pediatric; high-grade glioma; DIPG; therapeutics; epigenetics; clinical trial pediatric; high-grade glioma; DIPG; therapeutics; epigenetics; clinical trial
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Bailey, C.P.; Figueroa, M.; Mohiuddin, S.; Zaky, W.; Chandra, J. Cutting Edge Therapeutic Insights Derived from Molecular Biology of Pediatric High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG). Bioengineering 2018, 5, 88.

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