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Updated: Jul 9, 2025
Glioblastoma Relapse Post-Resection Model for Therapeutic Hydrogel Investigations
Published on: February 24, 2023
Acquired temozolomide resistance instructs patterns of glioblastoma behavior in gelatin hydrogels
Abstract:
Acquired drug resistance in glioblastoma (GBM) presents a major clinical challenge and is a key factor contributing to abysmal prognosis, with less than 15 months median overall survival. Aggressive chemotherapy with the frontline therapeutic, temozolomide (TMZ), ultimately fails to kill residual highly invasive tumor cells after surgical resection and radiotherapy. Here, we report a three-dimensional (3D) engineered model of acquired TMZ resistance using two isogenically-matched sets of GBM cell lines encapsulated in gelatin methacrylol hydrogels. We benchmark response of TMZ-resistant vs. TMZ-sensitive GBM cell lines within the gelatin-based extracellular matrix platform and further validate drug response at physiologically relevant TMZ concentrations. We show changes in drug sensitivity, cell invasion, and matrix-remodeling cytokine production as the result of acquired TMZ resistance. This platform lays the foundation for future investigations targeting key elements of the GBM tumor microenvironment to combat GBM's devastating impact by advancing our understanding of GBM progression and treatment response to guide the development of novel treatment strategies.
Teaser:
A hydrogel model to investigate the impact of acquired drug resistance on functional response in glioblastoma.
Insights
Acquired drug resistance in glioblastoma (GBM) is a major challenge. A new 3D hydrogel model helps study temozolomide (TMZ) resistance, revealing changes in cell invasion and cytokine production to guide future treatments.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Neuro-oncology
Background:
- Acquired drug resistance in glioblastoma (GBM) significantly worsens patient prognosis, with median survival under 15 months.
- Frontline chemotherapy, temozolomide (TMZ), often fails against residual invasive GBM cells post-surgery and radiotherapy.
Conclusions:
- The developed 3D hydrogel platform provides a valuable tool for studying acquired drug resistance in GBM.
- Understanding the tumor microenvironment's role in GBM progression and treatment response is crucial.
- This model can guide the development of novel therapeutic strategies targeting GBM resistance mechanisms.
