Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma CANCER CELL Chen, X., Stewart, E., Shelat, A. A., Qu, C., Bahrami, A., Hatley, M., Wu, G., Bradley, C., McEvoy, J., Pappo, A., Spunt, S., Valentine, M. B., Valentine, V., Krafcik, F., Lang, W. H., Wierdl, M., Tsurkan, L., Tolleman, V., Federico, S. M., Morton, C., Lu, C., Ding, L., Easton, J., Rusch, M., Nagahawatte, P., Wang, J., Parker, M., Wei, L., Hedlund, E., Finkelstein, D., Edmonson, M., Shurtleff, S., Boggs, K., Mulder, H., Yergeau, D., Skapek, S., Hawkins, D. S., Ramirez, N., Potter, P. M., Sandoval, J. A., Davidoff, A. M., Mardis, E. R., Wilson, R. K., Zhang, J., Downing, J. R., Dyer, M. A. 2013; 24 (6): 710-724

Abstract

Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Rhabdomyosarcoma has two major histologic subtypes, embryonal and alveolar, each with distinct clinical, molecular, and genetic features. Genomic analysis shows that embryonal tumors have more structural and copy number variations than alveolar tumors. Mutations in the RAS/NF1 pathway are significantly associated with intermediate- and high-risk embryonal rhabdomyosarcomas (ERMS). In contrast, alveolar rhabdomyosarcomas (ARMS) have fewer genetic lesions overall and no known recurrently mutated cancer consensus genes. To identify therapeutics for ERMS, we developed and characterized orthotopic xenografts of tumors that were sequenced in our study. High-throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for ERMS.

View details for DOI 10.1016/j.ccr.2013.11.002

View details for Web of Science ID 000328443200006

View details for PubMedID 24332040

View details for PubMedCentralID PMC3904731