Skaga , E , Kulesskiy , E , Fayzullin , A , Sandberg , C J , Potdar , S , Kyttälä , A , Langmoen , I A , Laakso , A , Gaal-Paavola , E , Perola , M , Wennerberg , K & Vik-Mo , E O 2019 , ' Intertumoral heterogeneity in patient-specific drug sensitivities in treatment-naive glioblastoma ' , BMC Cancer , vol. 19 , 628 . https://doi.org/10.1186/s12885-019-5861-4
Title: | Intertumoral heterogeneity in patient-specific drug sensitivities in treatment-naive glioblastoma |
Author: | Skaga, Erlend; Kulesskiy, Evgeny; Fayzullin, Artem; Sandberg, Cecilie J.; Potdar, Swapnil; Kyttälä, Aija; Langmoen, Iver A.; Laakso, Aki; Gaal-Paavola, Emilia; Perola, Markus; Wennerberg, Krister; Vik-Mo, Einar O. |
Contributor organization: | Institute for Molecular Medicine Finland University of Helsinki Department of Neurosciences Neurokirurgian yksikkö HUS Neurocenter Krister Wennerberg / Principal Investigator |
Date: | 2019-06-25 |
Language: | eng |
Number of pages: | 14 |
Belongs to series: | BMC Cancer |
ISSN: | 1471-2407 |
DOI: | https://doi.org/10.1186/s12885-019-5861-4 |
URI: | http://hdl.handle.net/10138/310764 |
Abstract: | BackgroundA major barrier to effective treatment of glioblastoma (GBM) is the large intertumoral heterogeneity at the genetic and cellular level. In early phase clinical trials, patient heterogeneity in response to therapy is commonly observed; however, how tumor heterogeneity is reflected in individual drug sensitivities in the treatment-naive glioblastoma stem cells (GSC) is unclear.MethodsWe cultured 12 patient-derived primary GBMs as tumorspheres and validated tumor stem cell properties by functional assays. Using automated high-throughput screening (HTS), we evaluated sensitivity to 461 anticancer drugs in a collection covering most FDA-approved anticancer drugs and investigational compounds with a broad range of molecular targets. Statistical analyses were performed using one-way ANOVA and Spearman correlation.ResultsAlthough tumor stem cell properties were confirmed in GSC cultures, their in vitro and in vivo morphology and behavior displayed considerable tumor-to-tumor variability. Drug screening revealed significant differences in the sensitivity to anticancer drugs (p |
Subject: |
Glioblastoma
Glioblastoma stem cells High-throughput drug screening Individualized medicine Drug sensitivity Functional precision medicine GLIOMA STEM-CELLS PHASE-II INITIATING CELLS OPEN-LABEL TEMOZOLOMIDE RECURRENT MEDICINE RADIOTHERAPY DISULFIRAM INHIBITOR 3122 Cancers |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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