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

Jennifer Xavier, 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 journalArticle

74 Citations (Scopus)

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 (US)
Pages (from-to)384-399
Number of pages16
JournalCancer Cell
Volume20
Issue number3
DOIs
StatePublished - Sep 1 2011

Fingerprint

Ependymoma
Centrosome
Neural Stem Cells
Brain Neoplasms
Fluorouracil
Phosphotransferases
Cell Proliferation
In Vitro Techniques
Insulin
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Xavier, J., Shelat, A. A., Carcaboso, A. M., Kranenburg, T. A., Arnold, L. A., Boulos, N., ... Gilbertson, R. J. (2011). An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma. Cancer Cell, 20(3), 384-399. https://doi.org/10.1016/j.ccr.2011.08.013
Xavier, Jennifer ; Shelat, Anang A. ; Carcaboso, Angel Montero ; Kranenburg, Tanya A. ; Arnold, Leggy A. ; Boulos, Nidal ; Wright, Karen ; Johnson, Robert A. ; Poppleton, Helen ; Mohankumar, Kumarasamypet M. ; Féau, Clementine ; Phoenix, Timothy ; Gibson, Paul ; Zhu, Liqin ; Tong, Yiai ; Eden, Chris ; Ellison, David W. ; Priebe, Waldemar ; Koul, Dimpy ; Yung, W. K.Alfred ; Gajjar, Amar ; Stewart, Clinton F. ; Guy, R. Kiplin ; Gilbertson, Richard J. / An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma. In: Cancer Cell. 2011 ; Vol. 20, No. 3. pp. 384-399.
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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.",
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Xavier, J, Shelat, AA, Carcaboso, AM, Kranenburg, TA, Arnold, LA, Boulos, N, Wright, K, Johnson, RA, Poppleton, H, Mohankumar, KM, Féau, C, Phoenix, T, Gibson, P, Zhu, L, Tong, Y, Eden, C, Ellison, DW, Priebe, W, Koul, D, Yung, WKA, Gajjar, A, Stewart, CF, Guy, RK & Gilbertson, RJ 2011, 'An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma', Cancer Cell, vol. 20, no. 3, pp. 384-399. https://doi.org/10.1016/j.ccr.2011.08.013

An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma. / Xavier, Jennifer; Shelat, Anang A.; Carcaboso, Angel Montero; Kranenburg, Tanya A.; Arnold, Leggy A.; Boulos, Nidal; Wright, Karen; Johnson, Robert A.; Poppleton, Helen; Mohankumar, Kumarasamypet M.; Féau, Clementine; Phoenix, Timothy; Gibson, Paul; Zhu, Liqin; Tong, Yiai; Eden, Chris; Ellison, David W.; Priebe, Waldemar; Koul, Dimpy; Yung, W. K.Alfred; Gajjar, Amar; Stewart, Clinton F.; Guy, R. Kiplin; Gilbertson, Richard J.

In: Cancer Cell, Vol. 20, No. 3, 01.09.2011, p. 384-399.

Research output: Contribution to journalArticle

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T1 - An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma

AU - Xavier, Jennifer

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.

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Xavier J, Shelat AA, Carcaboso AM, Kranenburg TA, Arnold LA, Boulos N et al. An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma. Cancer Cell. 2011 Sep 1;20(3):384-399. https://doi.org/10.1016/j.ccr.2011.08.013