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Updated: Sep 27, 2025
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid
Hui Xia1, Naze G Avci1, Yasemin Akay1
11 Biomedical Engineering DepartmentUniversity of Houston Houston TX 77204 USA.
Abstract:
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, accounting for 50% of all cases. GBM patients have a five-year survival rate of merely 5.6% and a median overall survival of 14.6 months with the "Stupp" regimen, 20.9 months with tumor treatment fields (TTF, OptuneR) in patients who participated in clinical trials, and 11 months for all GBM patients prior to TTF use. Objective: Our group recently developed a brain cancer chip which generates tumor spheroids, and provides large-scale assessments on the response of tumor cells to various concentrations and combinations of drugs. This platform could optimize the use of tumor samples derived from GBM patients to provide valuable insight on the tumor growth and responses to drug therapies. To minimize any sample loss in vitro, we improved our brain cancer chip system by adding an additional laminar flow distribution layer, which reduces sample loss during cell seeding and prevents spheroids from escaping from the microwells. Methods: In this study, we cultured 3D spheroids from GBM cell lines and patient-derived GBM cells in vitro, and investigated the effect of the combination of Temozolomide and nuclear factor-κB inhibitor on tumor growth. Results: Our study revealed that these drugs have synergistic effects in inhibiting spheroid formation when used in combination. Conclusions: These results suggest that the brain cancer chip enables large-scale, inexpensive and sample-effective drug screening to 3D cancer tumors in vitro, and could be applied to related tissue engineering drug screening studies.
Insights
A novel brain cancer chip effectively screens drug combinations for glioblastoma (GBM) by culturing 3D tumor spheroids. The chip demonstrated synergistic effects of Temozolomide and a nuclear factor-κB inhibitor, offering a promising platform for personalized GBM treatment strategies.
Area of Science:
- Neuro-oncology
- Biotechnology
- Drug Discovery
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with poor survival rates.
- Current treatments like the Stupp regimen and tumor treatment fields (TTF) offer limited efficacy.
- There is a need for advanced platforms to test drug responses in patient-derived GBM models.
Purpose of the Study:
- To develop and validate an improved brain cancer chip for large-scale drug screening.
- To assess the efficacy of drug combinations on 3D GBM spheroids.
- To optimize the use of patient-derived GBM samples for in vitro drug testing.
Main Methods:
- Cultured 3D spheroids from GBM cell lines and patient-derived cells in an enhanced brain cancer chip.
- Introduced a laminar flow distribution layer to minimize sample loss and spheroid escape.
- Investigated the combined effect of Temozolomide and a nuclear factor-κB inhibitor on spheroid growth.
Main Results:
- The enhanced brain cancer chip successfully cultured and maintained GBM spheroids.
- The combination of Temozolomide and the nuclear factor-κB inhibitor showed synergistic effects in inhibiting spheroid formation.
- The platform demonstrated sample-effective and large-scale drug screening capabilities.
Conclusions:
- The improved brain cancer chip is a valuable tool for in vitro drug screening of 3D GBM tumors.
- This platform can optimize drug testing using patient-derived samples, potentially leading to personalized treatment strategies.
- The chip technology holds promise for tissue engineering and related drug screening applications.
