Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomas

Pediatric high-grade gliomas (pHGGs) are the most common brain malignancies in children and are characterized by blocked differentiation. The epigenetic landscape of pHGGs, particularly the H3K27-altered and H3G34-mutant subtypes, suggests these tumors may be particularly susceptible to strategies t...

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Main Authors: Wang Xiang, Xiaolin Zhang, Minhai Dong, Lijun Wan, Bin Zhang, Feng Wan
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Pharmacological Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S1043661825000246
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author Wang Xiang
Xiaolin Zhang
Minhai Dong
Lijun Wan
Bin Zhang
Feng Wan
author_facet Wang Xiang
Xiaolin Zhang
Minhai Dong
Lijun Wan
Bin Zhang
Feng Wan
author_sort Wang Xiang
collection DOAJ
description Pediatric high-grade gliomas (pHGGs) are the most common brain malignancies in children and are characterized by blocked differentiation. The epigenetic landscape of pHGGs, particularly the H3K27-altered and H3G34-mutant subtypes, suggests these tumors may be particularly susceptible to strategies that target blocked differentiation. Differentiation therapy aims to overcome this differentiation blockade by promoting glioma cell differentiation into more mature and less malignant cells. Epigenetic modulators, including inhibitors of histone deacetylase (HDAC), enhancer of zeste homolog 2 (EZH2), BRG1/BRM-associated factor (BAF) complex, have shown promise in preclinical studies of pHGGs by altering the differentiation program of glioma cells. Although challenges remain in overcoming tumor cell heterogeneity, induced differentiation therapy holds promise for treating these currently incurable pediatric brain cancers.
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publishDate 2025-02-01
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series Pharmacological Research
spelling doaj-art-79bb95e3b36a4c3980deb3fef7db821e2025-02-08T04:59:47ZengElsevierPharmacological Research1096-11862025-02-01212107599Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomasWang Xiang0Xiaolin Zhang1Minhai Dong2Lijun Wan3Bin Zhang4Feng Wan5Department of Neurosurgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430030, PR ChinaDepartment of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, PR ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, PR China; Postdoctoral Research Station, School of Basic Medicine Science, Guangxi Medical University, Nanning 530021, PR ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of The Third Army Medical University, Chongqing 404100, PR ChinaDepartment of Physiology, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430030, PR China; Corresponding authors.Department of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, PR China; Corresponding authors.Pediatric high-grade gliomas (pHGGs) are the most common brain malignancies in children and are characterized by blocked differentiation. The epigenetic landscape of pHGGs, particularly the H3K27-altered and H3G34-mutant subtypes, suggests these tumors may be particularly susceptible to strategies that target blocked differentiation. Differentiation therapy aims to overcome this differentiation blockade by promoting glioma cell differentiation into more mature and less malignant cells. Epigenetic modulators, including inhibitors of histone deacetylase (HDAC), enhancer of zeste homolog 2 (EZH2), BRG1/BRM-associated factor (BAF) complex, have shown promise in preclinical studies of pHGGs by altering the differentiation program of glioma cells. Although challenges remain in overcoming tumor cell heterogeneity, induced differentiation therapy holds promise for treating these currently incurable pediatric brain cancers.http://www.sciencedirect.com/science/article/pii/S1043661825000246Pediatric high-grade gliomaDifferentiation therapyEpigenetic regulation
spellingShingle Wang Xiang
Xiaolin Zhang
Minhai Dong
Lijun Wan
Bin Zhang
Feng Wan
Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomas
Pharmacological Research
Pediatric high-grade glioma
Differentiation therapy
Epigenetic regulation
title Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomas
title_full Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomas
title_fullStr Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomas
title_full_unstemmed Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomas
title_short Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomas
title_sort differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high grade gliomas
topic Pediatric high-grade glioma
Differentiation therapy
Epigenetic regulation
url http://www.sciencedirect.com/science/article/pii/S1043661825000246
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