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

Jennifer M. Atkinson, Anang A. Shelat, Angel Montero Carcaboso, Tanya A. Kranenburg, Leggy A. Arnold, Nidal Boulos, Karen Wright, Robert A. Johnson, Helen Poppleton, Kumarasamypet M. Mohankumar, Clementine Féau, Timothy Phoenix, Paul Gibson, Liqin Zhu, Yiai Tong, Chris Eden, David W. Ellison, Waldemar Priebe, Dimpy Koul, W. K.Alfred YungAmar Gajjar, Clinton F. Stewart, R. Kiplin Guy, Richard J. Gilbertson

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

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.

Original languageEnglish
Pages (from-to)384-399
Number of pages16
JournalCancer Cell
Volume20
Issue number3
DOIs
StatePublished - Sep 2011

Bibliographical note

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.

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma'. Together they form a unique fingerprint.

Cite this