Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor, characterized by its aggressive behavior, limited treatment options, and poor prognosis. Despite advances in surgery, radiotherapy, and chemotherapy, the median survival of GBM patients remains disappointingly short. Recen...

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Main Authors: Li Zhang, Yang Yang, Yanchu Li, Chenyu Wang, Chenbin Bian, Hongbin Wang, Feng Wang
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Biomarker Research
Subjects:
Online Access:https://doi.org/10.1186/s40364-025-00788-w
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author Li Zhang
Yang Yang
Yanchu Li
Chenyu Wang
Chenbin Bian
Hongbin Wang
Feng Wang
author_facet Li Zhang
Yang Yang
Yanchu Li
Chenyu Wang
Chenbin Bian
Hongbin Wang
Feng Wang
author_sort Li Zhang
collection DOAJ
description Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor, characterized by its aggressive behavior, limited treatment options, and poor prognosis. Despite advances in surgery, radiotherapy, and chemotherapy, the median survival of GBM patients remains disappointingly short. Recent studies have underscored the critical role of histone modifications in GBM malignant progression and therapy resistance. Histones, protein components of chromatin, undergo various modifications, including acetylation and methylation. These modifications significantly affect gene expression, thereby promoting tumorigenesis and resistance to therapy. Targeting histone modifications has emerged as a promising therapeutic approach. Numerous pre-clinical studies have evaluated histone modification agents in GBM, including histone deacetylase inhibitors and histone methyltransferase inhibitors. These studies demonstrate that modulating histone modifications can alter gene expression patterns, inhibit tumor growth, induce apoptosis, and sensitize tumor cells to conventional treatments. Some agents have advanced to clinical trials, aiming to translate preclinical efficacy into clinical benefit. However, clinical outcomes remain suboptimal, as many agents fail to significantly improve GBM patient prognosis. These challenges are attributed to the complexity of histone modification networks and the adaptive responses of the tumor microenvironment. This review provides a comprehensive overview of epigenetic regulation mechanisms involving histone modifications in GBM, covering their roles in tumor development, tumor microenvironment remodeling, and therapeutic resistance. Additionally, the review discusses current clinical trials targeting histone modifications in GBM, highlighting successes, limitations, and future perspectives.
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spelling doaj-art-c554e5aa93104a9dab56a54bf95d89bb2025-08-20T03:22:07ZengBMCBiomarker Research2050-77712025-05-0113113210.1186/s40364-025-00788-wEpigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insightsLi Zhang0Yang Yang1Yanchu Li2Chenyu Wang3Chenbin Bian4Hongbin Wang5Feng Wang6Division of Head & Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan UniversityDivision of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan UniversityDivision of Head & Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan UniversityYuexiu District, First Affiliated Hospital of Sun Yat-Sen UniversityDivision of Head & Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan UniversityDivision of Head & Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan UniversityDivision of Head & Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan UniversityAbstract Glioblastoma (GBM) is the most common primary malignant brain tumor, characterized by its aggressive behavior, limited treatment options, and poor prognosis. Despite advances in surgery, radiotherapy, and chemotherapy, the median survival of GBM patients remains disappointingly short. Recent studies have underscored the critical role of histone modifications in GBM malignant progression and therapy resistance. Histones, protein components of chromatin, undergo various modifications, including acetylation and methylation. These modifications significantly affect gene expression, thereby promoting tumorigenesis and resistance to therapy. Targeting histone modifications has emerged as a promising therapeutic approach. Numerous pre-clinical studies have evaluated histone modification agents in GBM, including histone deacetylase inhibitors and histone methyltransferase inhibitors. These studies demonstrate that modulating histone modifications can alter gene expression patterns, inhibit tumor growth, induce apoptosis, and sensitize tumor cells to conventional treatments. Some agents have advanced to clinical trials, aiming to translate preclinical efficacy into clinical benefit. However, clinical outcomes remain suboptimal, as many agents fail to significantly improve GBM patient prognosis. These challenges are attributed to the complexity of histone modification networks and the adaptive responses of the tumor microenvironment. This review provides a comprehensive overview of epigenetic regulation mechanisms involving histone modifications in GBM, covering their roles in tumor development, tumor microenvironment remodeling, and therapeutic resistance. Additionally, the review discusses current clinical trials targeting histone modifications in GBM, highlighting successes, limitations, and future perspectives.https://doi.org/10.1186/s40364-025-00788-wGlioblastomaHistone modificationsHistone acetylationHistone methylationGlioblastoma chemoresistance
spellingShingle Li Zhang
Yang Yang
Yanchu Li
Chenyu Wang
Chenbin Bian
Hongbin Wang
Feng Wang
Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights
Biomarker Research
Glioblastoma
Histone modifications
Histone acetylation
Histone methylation
Glioblastoma chemoresistance
title Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights
title_full Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights
title_fullStr Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights
title_full_unstemmed Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights
title_short Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights
title_sort epigenetic regulation of histone modifications in glioblastoma recent advances and therapeutic insights
topic Glioblastoma
Histone modifications
Histone acetylation
Histone methylation
Glioblastoma chemoresistance
url https://doi.org/10.1186/s40364-025-00788-w
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AT chenyuwang epigeneticregulationofhistonemodificationsinglioblastomarecentadvancesandtherapeuticinsights
AT chenbinbian epigeneticregulationofhistonemodificationsinglioblastomarecentadvancesandtherapeuticinsights
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