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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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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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
- Atypical teratoid rhabdoid tumor
- Aurora Kinase A