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Updated: Nov 28, 2025
Co-culture of Glioblastoma Stem-like Cells on Patterned Neurons to Study Migration and Cellular Interactions
Published on: February 24, 2021
Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance
Zulfikar Azam1,2, Shing-Shun Tony To2, Bakhos A Tannous1
1Experimental Therapeutics and Molecular Imaging Unit Department of Neurology Neuro-Oncology Division Massachusetts General Hospital and Harvard Medical School Boston MA 02129 USA.
Abstract:
Despite decades of research, glioblastoma (GBM) remains invariably fatal among all forms of cancers. The high level of inter- and intratumoral heterogeneity along with its biological location, the brain, are major barriers against effective treatment. Molecular and single cell analysis identifies different molecular subtypes with varying prognosis, while multiple subtypes can reside in the same tumor. Cellular plasticity among different subtypes in response to therapies or during recurrence adds another hurdle in the treatment of GBM. This phenotypic shift is induced and sustained by activation of several pathways within the tumor itself, or microenvironmental factors. In this review, the dynamic nature of cellular shifts in GBM and how the tumor (immune) microenvironment shapes this process leading to therapeutic resistance, while highlighting emerging tools and approaches to study this dynamic double-edged sword are discussed.
Insights
Glioblastoma (GBM) is a fatal brain cancer due to its heterogeneity and cellular plasticity. Understanding how the tumor microenvironment drives these shifts is key to overcoming therapeutic resistance.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Tumor Microenvironment
Background:
- Glioblastoma (GBM) remains a highly lethal brain cancer despite extensive research.
- Tumor heterogeneity and brain location present significant treatment challenges.
- Multiple molecular subtypes exist within GBM, contributing to varied prognoses and treatment responses.
Purpose of the Study:
- To review the dynamic cellular shifts in glioblastoma.
- To explore the role of the tumor microenvironment in driving these changes.
- To highlight emerging methods for studying GBM's complex cellular dynamics.
Main Methods:
- Review of current literature on glioblastoma cellular plasticity.
- Analysis of molecular and single-cell studies identifying GBM subtypes.
- Discussion of the impact of tumor microenvironment and therapeutic resistance.
Main Results:
- GBM exhibits significant inter- and intratumoral heterogeneity.
- Cellular plasticity allows GBM to adapt to therapies and recur.
- The tumor (immune) microenvironment significantly influences cellular shifts and therapeutic resistance.
Conclusions:
- Cellular plasticity and microenvironmental factors are critical hurdles in glioblastoma treatment.
- Targeting these dynamic processes and utilizing novel research tools are essential for improving outcomes.
- Further research into the interplay between GBM cells and their microenvironment is crucial for developing effective therapies.
