Targeting Aurora Kinase A enhances radiation sensitivity of atypical teratoid rhabdoid tumor cells |
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| Authors: | Sujatha Venkataraman Irina Alimova Tiffany Tello Peter S. Harris Jeffrey A. Knipstein Andrew M. Donson Nicholas K. Foreman Arthur K. Liu Rajeev Vibhakar |
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| Affiliation: | (1) Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA;(2) University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA;(3) Department of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA;(4) Department of Pediatrics, University of Colorado Denver, 12800 19th Ave, Mail Stop 8302, Aurora, CO 80045, USA; |
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| Abstract: | 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. |
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