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Updated: Dec 31, 2025
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Feasibility study of using high-throughput drug sensitivity testing to target recurrent glioblastoma stem cells for
Erlend Skaga1,2, Evgeny Kulesskiy3, Marit Brynjulvsen4,5
1Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway. erlend.skaga@gmail.com.
Background:
Despite the well described heterogeneity in glioblastoma (GBM), treatment is standardized, and clinical trials investigate treatment effects at population level. Genomics-driven oncology for stratified treatments allow clinical decision making in only a small minority of screened patients. Addressing tumor heterogeneity, we aimed to establish a clinical translational protocol in recurrent GBM (recGBM) utilizing autologous glioblastoma stem cell (GSC) cultures and automated high-throughput drug sensitivity and resistance testing (DSRT) for individualized treatment within the time available for clinical application.
Results:
From ten patients undergoing surgery for recGBM, we established individual cell cultures and characterized the GSCs by functional assays. 7/10 GSC cultures could be serially expanded. The individual GSCs displayed intertumoral differences in their proliferative capacity, expression of stem cell markers and variation in their in vitro and in vivo morphology. We defined a time frame of 10 weeks from surgery to complete the entire pre-clinical work-up; establish individualized GSC cultures, evaluate drug sensitivity patterns of 525 anticancer drugs, and identify options for individualized treatment. Within the time frame for clinical translation 5/7 cultures reached sufficient cell yield for complete drug screening. The DSRT revealed significant intertumoral heterogeneity to anticancer drugs (p < 0.0001). Using curated reference databases of drug sensitivity in GBM and healthy bone marrow cells, we identified individualized treatment options in all patients. Individualized treatment options could be selected from FDA-approved drugs from a variety of different drug classes in all cases.
Conclusions:
In recGBM, GSC cultures could successfully be established in the majority of patients. The individual cultures displayed intertumoral heterogeneity in their in vitro and in vivo behavior. Within a time frame for clinical application, we could perform DSRT in 50% of recGBM patients. The DSRT revealed a remarkable intertumoral heterogeneity in sensitivity to anticancer drugs in recGBM that could allow tailored therapeutic options for functional precision medicine.
Insights
This study shows that glioblastoma stem cell cultures can be established from recurrent tumors and tested for drug sensitivity. This approach identifies personalized treatment options for patients within a clinically relevant timeframe.
Area of Science:
- Oncology
- Cancer Research
- Translational Medicine
Background:
- Glioblastoma (GBM) exhibits significant heterogeneity, yet treatments remain standardized.
- Current genomic approaches enable personalized treatment for only a small fraction of patients.
- Tumor heterogeneity poses a challenge for effective glioblastoma therapy.
Purpose of the Study:
- To establish a clinical protocol for recurrent glioblastoma (recGBM) using patient-derived glioblastoma stem cell (GSC) cultures.
- To implement automated high-throughput drug sensitivity and resistance testing (DSRT) for individualized treatment strategies.
- To assess the feasibility of individualized treatment within a clinically applicable timeframe.
Main Methods:
- Established individual GSC cultures from ten recGBM patients.
- Characterized GSCs using functional assays, assessing proliferative capacity, stem cell marker expression, and morphology.
- Performed automated DSRT on 525 anticancer drugs for each GSC culture.
Main Results:
- Successfully established serial GSC cultures from 7/10 patients.
- Demonstrated significant intertumoral heterogeneity in GSC behavior and drug sensitivity (p < 0.0001).
- Identified individualized treatment options using FDA-approved drugs for all patients within a 10-week preclinical workup period.
Conclusions:
- GSC cultures are feasible in the majority of recGBM patients, displaying intertumoral heterogeneity.
- Automated DSRT can be performed within a clinical timeframe, enabling personalized treatment selection.
- This approach facilitates functional precision medicine by revealing drug sensitivity heterogeneity in recGBM.
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