Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 30, Issue 9, Pages 1005-1014Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2010.31.8907
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Funding
- National Institutes of Health [R01 CA87637]
- Astra-Zeneca
- Sussman Family Fund
- Charles and Marjorie Holloway Foundation
- Breast Cancer Alliance
- Lerner Award
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The Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway was discovered 20 years ago as a mediator of cytokine signaling. Since this time, more than 2,500 articles have been published demonstrating the importance of this pathway in virtually all malignancies. Although there are dozens of cytokines and cytokine receptors, four Jaks, and seven Stats, it seems that interleukin-6-mediated activation of Stat3 is a principal pathway implicated in promoting tumorigenesis. This transcription factor regulates the expression of numerous critical mediators of tumor formation and metastatic progression. This review will examine the relative importance and function of this pathway in nonmalignant conditions as well as malignancies (including tumor intrinsic and extrinsic), the influence of other Stats, the development of inhibitors to this pathway, and the potential role of inhibitors in controlling or eradicating cancers. J Clin Oncol 30: 1005-1014. (C) 2012 by American Society of Clinical Oncology
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