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Updated: Oct 25, 2025

Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
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The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma

Qiong Wu1, Anders E Berglund2, Arnold B Etame1

  • 1Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.

International Journal of Molecular Sciences
|August 7, 2021
PubMed

Insights

Glioblastoma resistance to chemotherapy is driven by epigenetic changes. Targeting these epigenetic modifications offers a promising strategy to improve glioblastoma treatment outcomes.

Area of Science:

  • Oncology
  • Epigenetics
  • Cancer Biology

Background:

  • Glioblastoma (GBM) is a fatal brain cancer resistant to standard treatments.
  • Temozolomide (TMZ) efficacy is limited by rapid, epigenetically driven tumor resistance.
  • Novel therapies are needed to overcome GBM treatment resistance.

Purpose of the Study:

  • To review the role of epigenetic modifications in glioblastoma adaptive resistance.
  • To highlight the impact of epigenetic alterations on treatment outcomes.
  • To emphasize the therapeutic potential of targeting epigenetic mechanisms in GBM.

Main Methods:

  • Literature review of studies on glioblastoma epigenetics and therapy resistance.
  • Analysis of epigenetic mechanisms including DNA methylation, histone modifications, and chromatin remodeling.
  • Synthesis of current evidence on treatment-induced epigenetic changes.

Main Results:

  • Epigenetic modifications facilitate adaptive resistance evolution in GBM.
  • Treatment-induced epigenetic alterations enhance gene expression crucial for GBM survival.
  • DNA methylation, histone modifications, and chromatin remodeling are key mechanisms.

Conclusions:

  • Epigenetic modifications are central to glioblastoma's resistance to therapy.
  • Targeting epigenetic alterations is a critical priority for improving GBM treatment.
  • Understanding these mechanisms is essential for developing synergistic therapies.
Keywords:
DNA methylationchromatin remodelingepigenetic modificationsglioblastomahistone acetylationhistone methylationresistance

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