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

Wang Xiang; Xiaolin Zhang; Minhai Dong; Lijun Wan; Feng Wan; Bin Zhang

doi:10.1016/j.phrs.2025.107599

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

Pharmacol Res. 2025 Jan 14:107599. doi: 10.1016/j.phrs.2025.107599. Online ahead of print.

Authors

Wang Xiang¹, Xiaolin Zhang², Minhai Dong³, Lijun Wan⁴, Feng Wan⁵, Bin Zhang⁶

Affiliations

¹ Department of Neurosurgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, 430030, PR China. Electronic address: [email protected].
² Department of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, PR China. Electronic address: [email protected].
³ Department 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 China. Electronic address: [email protected].
⁴ Department of Neurosurgery, The Second Affiliated Hospital of The Third Army Medical University, Chongqing, 404100, PR China. Electronic address: [email protected].
⁵ Department of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, PR China. Electronic address: [email protected].
⁶ Department of Physiology, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, 430030, PR China. Electronic address: [email protected].

PMID: 39818258
DOI: 10.1016/j.phrs.2025.107599

Abstract

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.

Keywords: Differentiation therapy; Epigenetic regulation; Pediatric high-grade glioma.

Publication types

Review