Targeting Aurora Kinase A enhances radiation sensitivity of atypical teratoid rhabdoid tumor cells

被引：0

作者：

Sujatha Venkataraman

Irina Alimova

Tiffany Tello

Peter S. Harris

Jeffrey A. Knipstein

Andrew M. Donson

Nicholas K. Foreman

Arthur K. Liu

Rajeev Vibhakar

机构：

[1] University of Colorado School of Medicine,Department of Pediatrics, Children’s Hospital Colorado

[2] University of Colorado School of Medicine,Department of Radiation Oncology

[3] University of Colorado,Department of Pediatrics

[4] University of Colorado Denver,undefined

来源：

Journal of Neuro-Oncology | 2012年 / 107卷

关键词：

Atypical teratoid rhabdoid tumor; ATRT; Aurora Kinase A;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Atypical teratoid/rhabdoid tumors (ATRT) are rare, highly malignant, embryonal CNS tumors with a poor prognosis. Therapy relies on highly toxic chemotherapy and radiotherapy. To improve outcomes and decrease morbidity, more targeted therapy is required. Gene expression analysis revealed elevated expression of multiple kinases in ATRT tissues. Aurora Kinase A was one of the candidate kinases. The objective of this study was to evaluate the impact of Aurora Kinase A inhibition in ATRT cell lines. Our analysis revealed that inhibition of Aurora Kinase A induces cell death in ATRT cells and the small molecule inhibitor MLN 8237 sensitizes these cells to radiation. Furthermore, inhibition of Aurora Kinase A resulted in decreased activity of pro-proliferative signaling pathways. These data indicate that inhibition of Aurora Kinase A is a promising small molecule target for ATRT therapy.

引用

页码：517 / 526

页数：9

共 150 条

[1]

Bambakidis NC(2002)Atypical teratoid/rhabdoid tumors of the central nervous system: clinical, radiographic and pathologic features Pediatr Neurosurg 37 64-70

[2]

Robinson S(2004)Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry J Clin Oncol 22 2877-2884

[3]

Cohen M(2005)Atypical teratoid/rhabdoid tumors of the central nervous system J Neurooncol 75 309-313

[4]

Cohen AR(2008)Intensive induction chemotherapy followed by high dose chemotherapy with autologous hematopoietic progenitor cell rescue in young children newly diagnosed with central nervous system atypical teratoid rhabdoid tumors Pediatr Blood Cancer 51 235-240

[5]

Hilden JM(2009)Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor J Clin Oncol 27 385-389

[6]

Meerbaum S(1999)Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors Cancer Res 59 74-79

[7]

Burger P(2002)Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors Clin Cancer Res 8 3461-3467

[8]

Finlay J(2005)Cyclin D1 is overexpressed in atypical teratoid/rhabdoid tumor with hSNF5/INI1 gene inactivation J Neurooncol 73 117-124

[9]

Janss A(2006)Targeting tyrosine kinases in cancer: the second wave Science 312 1175-1178

[10]

Scheithauer BW(2010)Aurora kinase A as a rational target for therapy in glioblastoma J Neurosurg Pediatr 6 98-105

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