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Cancer Cell. 2011 Sep 13;20(3):384-99. doi: 10.1016/j.ccr.2011.08.013.

An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma.

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1
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

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.

PMID:
21907928
PMCID:
PMC3172881
DOI:
10.1016/j.ccr.2011.08.013
[Indexed for MEDLINE]
Free PMC Article
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