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

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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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Acknowledgments

The authors thank the Department of Pediatrics and The Children’s Hospital Denver for their support and Morgan Adams Foundation (to NF and RV); National Institutes of Health (KO8 NS59790 to RV) for funding.

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Authors and Affiliations

  1. Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA

    Sujatha Venkataraman, Irina Alimova, Peter S. Harris, Jeffrey A. Knipstein, Andrew M. Donson, Nicholas K. Foreman & Rajeev Vibhakar

  2. University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA

    Tiffany Tello

  3. Department of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA

    Arthur K. Liu

  4. Department of Pediatrics, University of Colorado Denver, 12800 19th Ave, Mail Stop 8302, Aurora, CO, 80045, USA

    Rajeev Vibhakar

Authors
  1. Sujatha Venkataraman
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  2. Irina Alimova
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  3. Tiffany Tello
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  4. Peter S. Harris
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  5. Jeffrey A. Knipstein
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  6. Andrew M. Donson
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  7. Nicholas K. Foreman
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  8. Arthur K. Liu
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  9. Rajeev Vibhakar
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Correspondence to Rajeev Vibhakar.

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Venkataraman, S., Alimova, I., Tello, T. et al. Targeting Aurora Kinase A enhances radiation sensitivity of atypical teratoid rhabdoid tumor cells. J Neurooncol 107, 517–526 (2012). https://doi.org/10.1007/s11060-011-0795-y

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  • DOI: https://doi.org/10.1007/s11060-011-0795-y

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