Intertumoral heterogeneity in patient-specific drug sensitivities in treatment-naive glioblastoma

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http://hdl.handle.net/10138/310764

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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: 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: 2019-06-25
Language: eng
Number of pages: 14
Belongs to series: BMC Cancer
ISSN: 1471-2407
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
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