Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma

Xiang Chen, Elizabeth Stewart, Anang A. Shelat, Chunxu Qu, Armita Bahrami, Mark Hatley, Gang Wu, Cori Bradley, Justina McEvoy, Alberto Pappo, Sheri Spunt, Marcus B. Valentine, Virginia Valentine, Fred Krafcik, Walter H. Lang, Monika Wierdl, Lyudmila Tsurkan, Viktor Tolleman, Sara M. Federico, Chris MortonCharles Lu, Li Ding, John Easton, Michael Rusch, Panduka Nagahawatte, Jianmin Wang, Matthew Parker, Lei Wei, Erin Hedlund, David Finkelstein, Michael Edmonson, Sheila Shurtleff, Kristy Boggs, Heather Mulder, Donald Yergeau, Steve Skapek, Douglas S. Hawkins, Nilsa Ramirez, Philip M. Potter, John A. Sandoval, Andrew M. Davidoff, Elaine R. Mardis, Richard K. Wilson, Jinghui Zhang, James R. Downing, Michael A. Dyer

Research output: Contribution to journalArticle

143 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)710-724
Number of pages15
JournalCancer Cell
Volume24
Issue number6
DOIs
StatePublished - Dec 9 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    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., ... Dyer, M. A. (2013). Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma. Cancer Cell, 24(6), 710-724. https://doi.org/10.1016/j.ccr.2013.11.002