Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma

Xiang Chen, Elizabeth Stewart, AnangA Shelat, Chunxu Qu, Armita Bahrami, Mark Hatley, Gang Wu, Cori Bradley, Justina McEvoy, Alberto Pappo, Sheri Spunt, MarcusB Valentine, Virginia Valentine, Fred Krafcik, WalterH Lang, Monika Wierdl, Lyudmila Tsurkan, Viktor Tolleman, SaraM Federico, Chris Morton & 26 others Charles 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, DouglasS Hawkins, Nilsa Ramirez, PhilipM Potter, JohnA Sandoval, AndrewM Davidoff, ElaineR Mardis, RichardK Wilson, Jinghui Zhang, JamesR Downing, MichaelA Dyer

Research output: Contribution to journalArticle

126 Citations (Scopus)

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

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Embryonal Rhabdomyosarcoma
Oxidative Stress
Rhabdomyosarcoma
Heterografts
Alveolar Rhabdomyosarcoma
Neoplasms
Neoplasm Genes
Sarcoma
Molecular Biology
Skeletal Muscle
Mutation
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Chen, X., Stewart, E., Shelat, A., Qu, C., Bahrami, A., Hatley, M., ... Dyer, M. (2013). Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma. Cancer Cell, 24(6), 710-724. https://doi.org/10.1016/j.ccr.2013.11.002

Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma. / Chen, Xiang; Stewart, Elizabeth; Shelat, AnangA; Qu, Chunxu; Bahrami, Armita; Hatley, Mark; Wu, Gang; Bradley, Cori; McEvoy, Justina; Pappo, Alberto; Spunt, Sheri; Valentine, MarcusB; Valentine, Virginia; Krafcik, Fred; Lang, WalterH; Wierdl, Monika; Tsurkan, Lyudmila; Tolleman, Viktor; Federico, SaraM; Morton, Chris; Lu, Charles; Ding, Li; Easton, John; Rusch, Michael; Nagahawatte, Panduka; Wang, Jianmin; Parker, Matthew; Wei, Lei; Hedlund, Erin; Finkelstein, David; Edmonson, Michael; Shurtleff, Sheila; Boggs, Kristy; Mulder, Heather; Yergeau, Donald; Skapek, Steve; Hawkins, DouglasS; Ramirez, Nilsa; Potter, PhilipM; Sandoval, JohnA; Davidoff, AndrewM; Mardis, ElaineR; Wilson, RichardK; Zhang, Jinghui; Downing, JamesR; Dyer, MichaelA.

In: Cancer Cell, Vol. 24, No. 6, 09.12.2013, p. 710-724.

Research output: Contribution to journalArticle

Chen, X, Stewart, E, Shelat, A, Qu, C, Bahrami, A, Hatley, M, Wu, G, Bradley, C, McEvoy, J, Pappo, A, Spunt, S, Valentine, M, Valentine, V, Krafcik, F, Lang, W, Wierdl, M, Tsurkan, L, Tolleman, V, Federico, S, 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, Ramirez, N, Potter, P, Sandoval, J, Davidoff, A, Mardis, E, Wilson, R, Zhang, J, Downing, J & Dyer, M 2013, 'Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma', Cancer Cell, vol. 24, no. 6, pp. 710-724. https://doi.org/10.1016/j.ccr.2013.11.002
Chen X, Stewart E, Shelat A, Qu C, Bahrami A, Hatley M et al. Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma. Cancer Cell. 2013 Dec 9;24(6):710-724. https://doi.org/10.1016/j.ccr.2013.11.002
Chen, Xiang ; Stewart, Elizabeth ; Shelat, AnangA ; Qu, Chunxu ; Bahrami, Armita ; Hatley, Mark ; Wu, Gang ; Bradley, Cori ; McEvoy, Justina ; Pappo, Alberto ; Spunt, Sheri ; Valentine, MarcusB ; Valentine, Virginia ; Krafcik, Fred ; Lang, WalterH ; Wierdl, Monika ; Tsurkan, Lyudmila ; Tolleman, Viktor ; Federico, SaraM ; Morton, Chris ; Lu, Charles ; Ding, Li ; Easton, John ; Rusch, Michael ; Nagahawatte, Panduka ; Wang, Jianmin ; Parker, Matthew ; Wei, Lei ; Hedlund, Erin ; Finkelstein, David ; Edmonson, Michael ; Shurtleff, Sheila ; Boggs, Kristy ; Mulder, Heather ; Yergeau, Donald ; Skapek, Steve ; Hawkins, DouglasS ; Ramirez, Nilsa ; Potter, PhilipM ; Sandoval, JohnA ; Davidoff, AndrewM ; Mardis, ElaineR ; Wilson, RichardK ; Zhang, Jinghui ; Downing, JamesR ; Dyer, MichaelA. / Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma. In: Cancer Cell. 2013 ; Vol. 24, No. 6. pp. 710-724.
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AU - Hatley, Mark

AU - Wu, Gang

AU - Bradley, Cori

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