Portal de Periódicos da CAPES

An Integrated In Vitro and In Vivo High-Throughput Screen Identifies Treatment Leads for Ependymoma

2011; Cell Press; Volume: 20; Issue: 3 Linguagem: Inglês

10.1016/j.ccr.2011.08.013

1878-3686

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

Histone Deacetylase Inhibitors Research

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.