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

被引：85

作者：

Atkinson, Jennifer M. ^{[1
]}

Shelat, Anang A. ^{[2
]}

Carcaboso, Angel Montero ^{[3
]}

Kranenburg, Tanya A. ^{[1
]}

Arnold, Leggy A. ^{[2
]}

Boulos, Nidal ^{[1
]}

Wright, Karen ^{[1
,4
]}

Johnson, Robert A. ^{[1
]}

Poppleton, Helen ^{[1
]}

Mohankumar, Kumarasamypet M. ^{[1
]}

Feau, Clementine ^{[2
]}

Phoenix, Timothy ^{[1
]}

Gibson, Paul ^{[1
]}

Zhu, Liqin ^{[1
]}

Tong, Yiai ^{[1
]}

Eden, Chris ^{[1
]}

Ellison, David W. ^{[5
]}

Priebe, Waldemar ^{[7
]}

Koul, Dimpy ^{[6
]}

Yung, W. K. Alfred ^{[6
]}

Gajjar, Amar ^{[4
]}

Stewart, Clinton F. ^{[3
]}

Guy, R. Kiplin ^{[2
]}

Gilbertson, Richard J. ^{[1
,4
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA

[3] St Jude Childrens Res Hosp, Dept Pharmacol, Memphis, TN 38105 USA

[4] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[5] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[6] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Neurooncol, Houston, TX 77030 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

来源：

CANCER CELL | 2011年 / 20卷 / 03期

基金：

美国国家卫生研究院;

关键词：

STEM-CELLS; HEDGEHOG PATHWAY; PHASE-I; IRINOTECAN; 5-FLUOROURACIL; MEDULLOBLASTOMA; TOPOTECAN; TUMORS; DOUBLECORTIN; MECHANISMS;

D O I：

10.1016/j.ccr.2011.08.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：384 / 399

页数：16

共 58 条

[11] Cyclin E-Cdk2 temporally regulates centrosome assembly and establishment of polarity in Caenorhabditis elegans embryos [J].

Cowan, Carrie R. ;

Hyman, Anthony A. .

NATURE CELL BIOLOGY, 2006, 8 (12) :1441-U82

[12]

Dietrich Joerg, 2006, J Biol, V5, P22, DOI 10.1186/jbiol50

[13] Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial [J].

Douillard, JY ;

Cunningham, D ;

Roth, AD ;

Navarro, M ;

James, RD ;

Karasek, P ;

Jandik, P ;

Iveson, T ;

Carmichael, J ;

Alakl, M ;

Gruia, G ;

Awad, L ;

Rougier, P .

LANCET, 2000, 355 (9209) :1041-1047

[14] EGFR tyrosine kinase inhibition radiosensitizes and induces apoptosis in malignant glioma and childhood ependymoma xenografts [J].

Geoerger, Birgit ;

Gaspar, Nathalie ;

Opolon, Panle ;

Morizet, Jackie ;

Devanz, Pauline ;

Lecluse, Yann ;

Valent, Alexander ;

Lacroix, Ludovic ;

Grill, Jacques ;

Vassal, Gilles .

INTERNATIONAL JOURNAL OF CANCER, 2008, 123 (01) :209-216

[15] Ependymomas in Adults [J].

Gilbert, Mark R. ;

Ruda, Roberta ;

Soffietti, Riccardo .

CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, 2010, 10 (03) :240-247

[16]

Gilbertson RJ, 2002, CLIN CANCER RES, V8, P3054

[17] Initial Testing (Stage 1) of Lapatinib by the Pediatric Preclinical Testing Program [J].

Gorlick, Richard ;

Kolb, E. Anders ;

Houghton, Peter J. ;

Morton, Christopher L. ;

Phelps, Doris ;

Schaiquevich, Paula ;

Stewart, Clinton ;

Keir, Stephen T. ;

Lock, Richard ;

Carol, Hernan ;

Reynolds, C. Patrick ;

Maris, John M. ;

Wu, Jianrong ;

Smith, Malcolm A. .

PEDIATRIC BLOOD & CANCER, 2009, 53 (04) :594-598

[18] Rationally Designed Pharmacogenomic Treatment Using Concurrent Capecitabine and Radiotherapy for Glioblastoma; Gene Expression Profiles Associated with Outcome [J].

Grunda, Jessica M. ;

Fiveash, John ;

Palmer, Cheryl A. ;

Cantor, Alan ;

Fathallah-Shaykh, Hassan M. ;

Nabors, L. Burt ;

Johnson, Martin R. .

CLINICAL CANCER RESEARCH, 2010, 16 (10) :2890-2898

[19] Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening [J].

Gupta, Piyush B. ;

Onder, Tamer T. ;

Jiang, Guozhi ;

Tao, Kai ;

Kuperwasser, Charlotte ;

Weinberg, Robert A. ;

Lander, Eric S. .

CELL, 2009, 138 (04) :645-659

[20]

Houghton JA, 1996, CLIN CANCER RES, V2, P107

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