Targeting Aurora Kinase A enhances radiation sensitivity of atypical teratoid rhabdoid tumor cells. J Neurooncol 2012 May;107(3):517-26
Date
01/17/2012Pubmed ID
22246202Pubmed Central ID
PMC4681522DOI
10.1007/s11060-011-0795-yScopus ID
2-s2.0-84864327872 (requires institutional sign-in at Scopus site) 51 CitationsAbstract
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.
Author List
Venkataraman S, Alimova I, Tello T, Harris PS, Knipstein JA, Donson AM, Foreman NK, Liu AK, Vibhakar RMESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsApoptosis
Aurora Kinase A
Aurora Kinases
Azepines
Blotting, Western
Central Nervous System Neoplasms
Enzyme Inhibitors
Gene Expression Profiling
Humans
Oligonucleotide Array Sequence Analysis
Pyrimidines
Radiation Tolerance
Real-Time Polymerase Chain Reaction
Rhabdoid Tumor
Teratoma
Tumor Cells, Cultured
