Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications

Glioblastoma (GBM), a highly aggressive and malignant form of primary adult brain cancer, poses significant therapeutic challenges. Despite our improved understanding of the cellular and molecular mechanisms underlying tumorigenesis and the evolution of GBM, targeted molecular therapies have failed...

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Main Authors: Farzaneh Amirmahani, Saurav Kumar, Sree Deepthi Muthukrishnan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Epigenetics and Epigenomics
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Online Access:https://www.frontiersin.org/articles/10.3389/freae.2025.1519449/full
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author Farzaneh Amirmahani
Saurav Kumar
Sree Deepthi Muthukrishnan
author_facet Farzaneh Amirmahani
Saurav Kumar
Sree Deepthi Muthukrishnan
author_sort Farzaneh Amirmahani
collection DOAJ
description Glioblastoma (GBM), a highly aggressive and malignant form of primary adult brain cancer, poses significant therapeutic challenges. Despite our improved understanding of the cellular and molecular mechanisms underlying tumorigenesis and the evolution of GBM, targeted molecular therapies have failed to improve patient survival outcomes. The failure of standard treatments and targeted therapies is mainly attributed to the acquisition of phenotypic plasticity of tumor cells and GBM stem-like cells. Epigenetic modifications and their mediators have emerged as crucial regulators of phenotypic plasticity, influencing tumor heterogeneity, therapy resistance and disease progression. Here, we summarize and provide insights into epigenetic regulation of GBM plasticity and specifically, focus on the roles played by DNA- and histone modifiers and non-coding RNAs in driving phenotypic plasticity and resistance. We also delve into their dynamics in response to standard therapies and the challenges for targeting them to overcome phenotypic plasticity and resistance in GBM.
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institution Kabale University
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publisher Frontiers Media S.A.
record_format Article
series Frontiers in Epigenetics and Epigenomics
spelling doaj-art-25d088917c3049be96cbf7ea845559b42025-08-20T03:49:46ZengFrontiers Media S.A.Frontiers in Epigenetics and Epigenomics2813-706X2025-05-01310.3389/freae.2025.15194491519449Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implicationsFarzaneh AmirmahaniSaurav KumarSree Deepthi MuthukrishnanGlioblastoma (GBM), a highly aggressive and malignant form of primary adult brain cancer, poses significant therapeutic challenges. Despite our improved understanding of the cellular and molecular mechanisms underlying tumorigenesis and the evolution of GBM, targeted molecular therapies have failed to improve patient survival outcomes. The failure of standard treatments and targeted therapies is mainly attributed to the acquisition of phenotypic plasticity of tumor cells and GBM stem-like cells. Epigenetic modifications and their mediators have emerged as crucial regulators of phenotypic plasticity, influencing tumor heterogeneity, therapy resistance and disease progression. Here, we summarize and provide insights into epigenetic regulation of GBM plasticity and specifically, focus on the roles played by DNA- and histone modifiers and non-coding RNAs in driving phenotypic plasticity and resistance. We also delve into their dynamics in response to standard therapies and the challenges for targeting them to overcome phenotypic plasticity and resistance in GBM.https://www.frontiersin.org/articles/10.3389/freae.2025.1519449/fullGBMepigeneticDNA methylationhistone modificationsnon-coding RNAsGBM stem-like cells
spellingShingle Farzaneh Amirmahani
Saurav Kumar
Sree Deepthi Muthukrishnan
Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications
Frontiers in Epigenetics and Epigenomics
GBM
epigenetic
DNA methylation
histone modifications
non-coding RNAs
GBM stem-like cells
title Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications
title_full Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications
title_fullStr Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications
title_full_unstemmed Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications
title_short Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications
title_sort epigenetic mechanisms of plasticity and resistance in glioblastoma therapeutic targets and implications
topic GBM
epigenetic
DNA methylation
histone modifications
non-coding RNAs
GBM stem-like cells
url https://www.frontiersin.org/articles/10.3389/freae.2025.1519449/full
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AT sauravkumar epigeneticmechanismsofplasticityandresistanceinglioblastomatherapeutictargetsandimplications
AT sreedeepthimuthukrishnan epigeneticmechanismsofplasticityandresistanceinglioblastomatherapeutictargetsandimplications