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Updated: Jul 14, 2026
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
A rapid assay for drug sensitivity of glioblastoma stem cells
Hilah Gal1, Arik Makovitzki, Ninette Amariglio
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Abstract:
Glioblastoma (GBM) is a highly infiltrating, aggressive brain cancer with no available curative treatment. We developed a rapid assay for assessing the effect of various drugs on GBM stem cells. The assay uses a small number of separated CD133+ cells (20,000 in 0.2 ml) in 96-well plate that form neurospheres within 1-2 days. Various drugs disperse the neurospheres within 24-36 h, which can be quantified microscopically. We used the GBM cell line A-172 to develop the conditions for the assay, utilizing Gleevec, the gamma-secretase inhibitor DAPT, and the anti-bacterial peptide amph1D. The results show dispersion of the neurospheres leading to cell death, at relatively low drugs concentrations (<25 microM). Drug combination showed a synergistic effect and disruption of neurospheres under lower concentrations. We applied this assay to the CD133+ cells of surgical specimens from three patients that showed similar results. This assay facilitates a rapid test of drugs on small amounts of fractionated patient's GBM stem cells.
Insights
This study introduces a fast assay to test drugs on glioblastoma (GBM) stem cells. The method effectively identifies drug treatments that disrupt GBM stem cell neurospheres, paving the way for new cancer therapies.
Area of Science:
- Oncology
- Stem Cell Biology
- Pharmacology
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with limited treatment options.
- GBM stem cells are crucial for tumor growth and recurrence.
- Effective drug screening for GBM stem cells is needed.
Purpose of the Study:
- To develop a rapid assay for evaluating drug efficacy on glioblastoma stem cells.
- To assess the potential of drug combinations for synergistic effects.
- To validate the assay using patient-derived GBM stem cells.
Main Methods:
- Utilized a small number of CD133+ GBM stem cells (20,000) in 96-well plates.
- Formed neurospheres within 1-2 days, which were then treated with various drugs.
- Quantified neurosphere dispersion and cell death microscopically within 24-36 hours.
- Tested drugs including Gleevec, DAPT, and amph1D, as well as drug combinations.
Main Results:
- The assay demonstrated effective dispersion of neurospheres and subsequent cell death at low drug concentrations (<25 microM).
- Drug combinations exhibited synergistic effects, disrupting neurospheres at even lower concentrations.
- The assay yielded similar results when applied to CD133+ cells from three different GBM patient surgical specimens.
Conclusions:
- A novel, rapid assay has been developed for testing drugs on glioblastoma stem cells.
- This assay allows for efficient drug screening using minimal amounts of fractionated patient GBM stem cells.
- The findings support the potential of this assay for personalized glioblastoma treatment strategies.
