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