Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma

被引：248

作者：

Chen, Xiang ^{[1
]}

Stewart, Elizabeth ^{[2
]}

Shelat, Anang A. ^{[3
]}

Qu, Chunxu ^{[1
]}

Bahrami, Armita ^{[4
]}

Hatley, Mark ^{[5
]}

Wu, Gang ^{[1
]}

Bradley, Cori ^{[2
]}

McEvoy, Justina ^{[2
]}

Pappo, Alberto ^{[5
]}

Spunt, Sheri ^{[5
]}

Valentine, Marcus B. ^{[6
]}

Valentine, Virginia ^{[6
]}

Krafcik, Fred ^{[2
]}

Lang, Walter H. ^{[7
]}

Wierdl, Monika ^{[3
]}

Tsurkan, Lyudmila ^{[3
]}

Tolleman, Viktor ^{[3
]}

Federico, Sara M. ^{[5
]}

Morton, Chris ^{[7
]}

Lu, Charles ^{[8
]}

Ding, Li ^{[8
,9
,10
,11
]}

Easton, John ^{[1
]}

Rusch, Michael ^{[1
]}

Nagahawatte, Panduka ^{[1
]}

Wang, Jianmin ^{[1
]}

Parker, Matthew ^{[1
]}

Wei, Lei ^{[1
]}

Hedlund, Erin ^{[1
]}

Finkelstein, David ^{[1
]}

Edmonson, Michael ^{[1
]}

Shurtleff, Sheila ^{[4
]}

Boggs, Kristy ^{[1
]}

Mulder, Heather ^{[1
]}

Yergeau, Donald ^{[1
]}

Skapek, Steve ^{[13
]}

Hawkins, Douglas S. ^{[14
]}

Ramirez, Nilsa ^{[12
]}

Potter, Philip M. ^{[3
]}

Sandoval, John A. ^{[7
]}

Davidoff, Andrew M. ^{[7
]}

Mardis, Elaine R. ^{[8
,9
,11
]}

Wilson, Richard K. ^{[8
,9
,11
]}

Zhang, Jinghui ^{[1
]}

Downing, James R. ^{[4
]}

Dyer, Michael A. ^{[2
,15
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

[3] St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA

[4] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[5] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[6] St Jude Childrens Res Hosp, Cytogenet Shared Resource, Memphis, TN 38105 USA

[7] St Jude Childrens Res Hosp, Dept Surg, Memphis, TN 38105 USA

[8] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA

[9] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA

[10] Washington Univ, Sch Med, Dept Med, St Louis, MO 63108 USA

[11] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63108 USA

[12] Nationwide Childrens Hosp, Columbus, OH 43205 USA

[13] Univ Texas SW Med Ctr Dallas, Div Pediat Hematol Oncol, Dallas, TX 75390 USA

[14] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, Div Hematol Oncol, Seattle, WA 98105 USA

[15] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

CANCER CELL | 2013年 / 24卷 / 06期

基金：

美国国家卫生研究院;

关键词：

HISTONE DEACETYLASE INHIBITORS; CELLS IN-VITRO; MUTATIONS; SURVIVAL; SARCOMA; NEUROBLASTOMA; FLAVOPIRIDOL; CARFILZOMIB; VORINOSTAT; EXPERIENCE;

D O I：

10.1016/j.ccr.2013.11.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：710 / 724

页数：15

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