REVIEW article
Front. Epigenet. Epigenom.
Sec. Chromatin Epigenomics
Volume 3 - 2025 | doi: 10.3389/freae.2025.1519449
This article is part of the Research TopicAberrations in Cancer Epigenomics in Primary and Metastatic Solid TumorsView all articles
Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications
Provisionally accepted
- University of Oklahoma Health Sciences Center, Oklahoma City, United States
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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.
Keywords: GBM, epigenetic, DNA Methylation, Histone Modifications, non-coding RNAs, GBM stem-like cells, phenotypic plasticity, therapeutic resistance
Received: 29 Oct 2024; Accepted: 06 May 2025.
Copyright: © 2025 Amirmahani, Kumar and Muthukrishnan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sree Deepthi Muthukrishnan, University of Oklahoma Health Sciences Center, Oklahoma City, United States
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