Feasibility study of using high-throughput drug sensitivity testing to target recurrent glioblastoma stem cells for individualized treatment

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http://hdl.handle.net/10138/310768

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Skaga , E , Kulesskiy , E , Brynjulvsen , M , Sandberg , C J , Potdar , S , Langmoen , I A , Laakso , A , Gaál-Paavola , E , Perola , M , Wennerberg , K & Vik-Mo , E O 2019 , ' Feasibility study of using high-throughput drug sensitivity testing to target recurrent glioblastoma stem cells for individualized treatment ' , Clinical and translational medicine , vol. 8 , no. 1 , 33 . https://doi.org/10.1186/s40169-019-0253-6

Title: Feasibility study of using high-throughput drug sensitivity testing to target recurrent glioblastoma stem cells for individualized treatment
Author: Skaga, Erlend; Kulesskiy, Evgeny; Brynjulvsen, Marit; Sandberg, Cecilie J; Potdar, Swapnil; Langmoen, Iver A; Laakso, Aki; Gaál-Paavola, Emília; Perola, Markus; Wennerberg, Krister; Vik-Mo, Einar O
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Department of Neurosciences
University of Helsinki, Neurokirurgian yksikkö
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Krister Wennerberg / Principal Investigator
Date: 2019-12-30
Language: eng
Number of pages: 15
Belongs to series: Clinical and translational medicine
ISSN: 2001-1326
URI: http://hdl.handle.net/10138/310768
Abstract: 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 
Subject: Drug sensitivity
Drug sensitivity and resistance testing
Glioblastoma
Glioblastoma stem cells
High-throughput drug screening
Individualized medicine
Recurrent glioblastoma
3112 Neurosciences
3126 Surgery, anesthesiology, intensive care, radiology
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