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J Clin Oncol. 2012 Mar 20;30(9):1005-14. doi: 10.1200/JCO.2010.31.8907. Epub 2012 Feb 21.

Targeting the interleukin-6/Jak/stat pathway in human malignancies.

Author information

1
Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, NY 10021, USA.

Abstract

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.

PMID:
22355058
PMCID:
PMC3341105
DOI:
10.1200/JCO.2010.31.8907
[Indexed for MEDLINE]
Free PMC Article

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