title: An in silico screen links gene expression signatures to drug response in glioblastoma stem cells.
abstract: Cancer stem cells (CSCs) are thought to promote resistance to chemotherapeutic drugs in glioblastoma, the most common and aggressive primary brain tumor. However, the use of high-throughput drug screens to discover novel small-molecule inhibitors for CSC has been hampered by their instability in long-term cell culture. We asked whether predictive models of drug response could be developed from gene expression signatures of established cell lines and applied to predict drug response in glioblastoma stem cells. Predictions for active compounds were confirmed both for 185 compounds in seven established glioma cell lines and 21 compounds in three glioblastoma stem cells. The use of established cell lines as a surrogate for drug response in CSC lines may enable the large-scale virtual screening of drug candidates that would otherwise be difficult or impossible to test directly in CSCs.
authors.affiliation: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: G
authors.initials: G
authors.lastname: Riddick
authors.affiliation: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.affiliation: Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Holbeck
authors.affiliation: Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Kopp
authors.affiliation: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Walling
authors.affiliation: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: NYU Brain Tumor Center, Laura and Isaac Perlmutter Cancer Center, Bellevue Hospital Cancer Center, New York University Langone Medical Center, New York, NY, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Fine
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002874:Chromosome Mapping / Q000379:methods; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D005189:False Positive Reactions; D015870:Gene Expression / Q000235:genetics*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D057166:High-Throughput Screening Assays; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011237:Predictive Value of Tests; D012334:RNA, Neoplasm / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D012334:RNA, Neoplasm