Functional temozolomide sensitivity testing of patient-specific glioblastoma stem cell cultures is predictive of clinical outcome

Autor: Erlend Skaga, Evgeny Kulesskiy, Swapnil Potdar, Ioannis Panagopoulos, Francesca Micci, Iver A. Langmoen, Cecilie J. Sandberg, Einar O. Vik-Mo
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Translational Oncology, Vol 26, Iss , Pp 101535- (2022)
Druh dokumentu: article
ISSN: 1936-5233
DOI: 10.1016/j.tranon.2022.101535
Popis: Serum-free culturing of patient-derived glioblastoma biopsies enrich for glioblastoma stem cells (GSCs) and is recognized as a disease-relevant model system in glioblastoma (GBM). We hypothesized that the temozolomide (TMZ) drug sensitivity of patient-derived GSC cultures correlates to clinical sensitivity patterns and has clinical predictive value in a cohort of GBM patients. To this aim, we established 51 individual GSC cultures from surgical biopsies from both treatment-naïve primary and pretreated recurrent GBM patients. The cultures were evaluated for sensitivity to TMZ over a dosing range achievable in normal clinical practice. Drug efficacy was quantified by the drug sensitivity score. MGMT-methylation status was investigated by pyrosequencing. Correlative, contingency, and survival analyses were performed for associations between experimental and clinical data. We found a heterogeneous response to temozolomide in the GSC culture cohort. There were significant differences in the sensitivity to TMZ between the newly diagnosed and the TMZ-treated recurrent disease (p
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