期刊
CANCER CELL
卷 17, 期 3, 页码 298-310出版社
CELL PRESS
DOI: 10.1016/j.ccr.2009.12.047
关键词
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资金
- NIH [U54CA112962, W81XWH-07-0408, R33CA128625, K12CA08772307, P50-CA105009, K08CA108748]
- DFCI
- Ovarian Cancer Research Fund
- ASCO Young Investigator Award and Prevent Cancer Foundation
- Deborah and Robert First
- Joel and Randi Cutler Ovarian Research Fund
- Aaron Foundation
Ovarian cancer is a leading cause of death from gynecologic malignancies. Treatment for advanced-stage disease remains limited and, to date, targeted therapies have been incompletely explored. By systematically suppressing each human tyrosine kinase in ovarian cancer cell lines by RNAi, we found that an autocrine signal-transducing loop involving NRG1 and activated ErbB3 operates in a subset of primary ovarian cancers and ovarian cancer cell lines. Perturbation of this circuit with ErbB3-directed RNAi decreased cell growth in three-dimensional culture and resulted in decreased disease progression and prolonged survival in a xenograft mouse model of ovarian cancer. Furthermore, a monoclonal ErbB3-directed antibody (MM-121) also significantly inhibited tumor growth in vivo. These findings identify ErbB3 as a potential therapeutic target in ovarian cancer.
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