Journal of Neuro-Oncology

, Volume 107, Issue 3, pp 517–526

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

  • Sujatha Venkataraman
  • Irina Alimova
  • Tiffany Tello
  • Peter S. Harris
  • Jeffrey A. Knipstein
  • Andrew M. Donson
  • Nicholas K. Foreman
  • Arthur K. Liu
  • Rajeev Vibhakar
Laboratory Investigation

DOI: 10.1007/s11060-011-0795-y

Cite this article as:
Venkataraman, S., Alimova, I., Tello, T. et al. J Neurooncol (2012) 107: 517. doi:10.1007/s11060-011-0795-y

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.

Keywords

Atypical teratoid rhabdoid tumorATRTAurora Kinase A

Supplementary material

11060_2011_795_MOESM1_ESM.eps (791 kb)
Supplementary material 2 (EPS 792 kb)

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Sujatha Venkataraman
    • 1
  • Irina Alimova
    • 1
  • Tiffany Tello
    • 2
  • Peter S. Harris
    • 1
  • Jeffrey A. Knipstein
    • 1
  • Andrew M. Donson
    • 1
  • Nicholas K. Foreman
    • 1
  • Arthur K. Liu
    • 3
  • Rajeev Vibhakar
    • 1
    • 4
  1. 1.Department of Pediatrics, Children’s Hospital ColoradoUniversity of Colorado School of MedicineAuroraUSA
  2. 2.University of Colorado School of MedicineAuroraUSA
  3. 3.Department of Radiation OncologyUniversity of ColoradoAuroraUSA
  4. 4.Department of PediatricsUniversity of Colorado DenverAuroraUSA