TY - JOUR
T1 - An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma
AU - Atkinson, Jennifer M.
AU - Shelat, Anang A.
AU - Carcaboso, Angel Montero
AU - Kranenburg, Tanya A.
AU - Arnold, Leggy A.
AU - Boulos, Nidal
AU - Wright, Karen
AU - Johnson, Robert A.
AU - Poppleton, Helen
AU - Mohankumar, Kumarasamypet M.
AU - Féau, Clementine
AU - Phoenix, Timothy
AU - Gibson, Paul
AU - Zhu, Liqin
AU - Tong, Yiai
AU - Eden, Chris
AU - Ellison, David W.
AU - Priebe, Waldemar
AU - Koul, Dimpy
AU - Yung, W. K.Alfred
AU - Gajjar, Amar
AU - Stewart, Clinton F.
AU - Guy, R. Kiplin
AU - Gilbertson, Richard J.
N1 - Funding Information:
R.J.G. holds the Howard C. Schott Research Chair from the Malia's Cord Foundation. R.K.G. holds the Robert J. Ullrich Chair in Chemical Biology and Therapeutics. This work was supported by grants from the National Institutes of Health (R.J.G., R01CA129541, P01CA96832 and P30CA021765), and the Collaborative Ependymoma Research Network (R.J.G., R.K.G., C.F.S., W.K.A.Y., W.P.) and by the American Lebanese Syrian Associated Charities. We are grateful to the staff of the Hartwell Center for Bioinformatics and Biotechnology, the AIC and the ARC at St Jude Children's Research Hospital for technical assistance.
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2011.08.013
DO - 10.1016/j.ccr.2011.08.013
M3 - Article
C2 - 21907928
AN - SCOPUS:80052569769
SN - 1535-6108
VL - 20
SP - 384
EP - 399
JO - Cancer cell
JF - Cancer cell
IS - 3
ER -