ACTR-79. ESTABLISHMENT OF CLINICAL PROTOCOL TARGETING CANCER STEM CELLS IN RECURRENT GLIOBLASTOMA USING HIGH-THROUGHPUT DRUG SCREENING

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2017-11, Vol.19 (suppl_6), p.vi18-vi18
• Main Authors: Skaga, Erlend, Kulesskiy, Evgeny, Brynjulfsen, Marit, Sandberg, Cecilie Jonsgar, Kyttälä, Aija, Langmoen, Iver Arne, Laakso, Aki, Gaál-Paavola, Emília, Perola, Markus, Wennerberg, Krister, Vik-Mo, Einar Osland
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nox168.066

Despite aggressive multimodal oncological treatment, glioblastoma (GBM) disease progresses within 10 months. Due to the lack of treatment options for the relapsed disease, enrollment in clinical trials may be the best option. However, the fundamental preclinical studies leading to clinical investigation are primarily conducted using biological material from primary GBM, thus inadequately reflecting the biology of the recurrent disease. As only a minority of relapsed patients undergoes secondary surgery, little data exists of cancer stem cell (CSC) biology in recurrent GBM (recGBM). The purpose of the study was to establish a clinical protocol targeting patient-specific CSCs in recGBM for individualized therapy. We aimed to establish patient-specific cell cultures yielding >10 7 cells within 6 weeks following surgery to enable high-throughput drug sensitivity and resistance testing (DSRT) to guide individualized therapy decisions before evidence of further progression. Tumor biopsy from ten patients operated for recGBM were cultured under serum-free, growth factor-enriched conditions. Cultures were evaluated by (i) cell yield and (ii) stem cell properties by assays of self-renewal capacity, expression of stem cell markers, lineage-specific differentiation and in vivo tumor formation. We found that 5/10 recGBM cultures reached the pre-determined cell yield counted in two independent laboratories. Additionally, 2/10 samples formed tumorspheres, but did not generate sufficient cell numbers. Stem cell properties were confirmed by functional assays. The five cultures yielding >10 7 cells were evaluated for DSRT measuring cell viability and cytotoxicity to >520 FDA-approved and investigational oncological drugs, representing multiple classes of targeted therapies and conventional chemotherapeutics. In the majority of samples from recGBM, patient-specific tumorsphere cultures enriched for CSCs can be established and propagated in serial passages. In the subset of patients to reach 10 7 cells we completed DSRT, allowing for an individualized evaluation of drug responses to be used in clinical decision-making and patient treatment.