title: An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma.
abstract: Using a mouse model of ependymoma-a chemoresistant brain tumor-we combined multicell high-throughput screening (HTS), kinome-wide binding assays, and in vivo efficacy studies, to identify potential treatments with predicted toxicity against neural stem cells (NSC). We identified kinases within the insulin signaling pathway and centrosome cycle as regulators of ependymoma cell proliferation, and their corresponding inhibitors as potential therapies. FDA approved drugs not currently used to treat ependymoma were also identified that posses selective toxicity against ependymoma cells relative to normal NSCs both in vitro and in vivo, e.g., 5-fluorouracil. Our comprehensive approach advances understanding of the biology and treatment of ependymoma including the discovery of several treatment leads for immediate clinical translation.
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Jennifer M
authors: JM
authors: Atkinson
authors: Anang A
authors: AA
authors: Shelat
authors: Angel Montero
authors: AM
authors: Carcaboso
authors: Tanya A
authors: TA
authors: Kranenburg
authors: Leggy A
authors: LA
authors: Arnold
authors: Nidal
authors: N
authors: Boulos
authors: Karen
authors: K
authors: Wright
authors: Robert A
authors: RA
authors: Johnson
authors: Helen
authors: H
authors: Poppleton
authors: Kumarasamypet M
authors: KM
authors: Mohankumar
authors: Clementine
authors: C
authors: Féau
authors: Timothy
authors: T
authors: Phoenix
authors: Paul
authors: P
authors: Gibson
authors: Liqin
authors: L
authors: Zhu
authors: Yiai
authors: Y
authors: Tong
authors: Chris
authors: C
authors: Eden
authors: David W
authors: DW
authors: Ellison
authors: Waldemar
authors: W
authors: Priebe
authors: Dimpy
authors: D
authors: Koul
authors: W K Alfred
authors: WK
authors: Yung
authors: Amar
authors: A
authors: Gajjar
authors: Clinton F
authors: CF
authors: Stewart
authors: R Kiplin
authors: RK
authors: Guy
authors: Richard J
authors: RJ
authors: Gilbertson
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004806:Ependymoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005472:Fluorouracil / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000379:methods*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D058953:Neural Stem Cells / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D001897:Boronic Acids; D007328:Insulin; D011719:Pyrazines; D000069286:Bortezomib; D005472:Fluorouracil