Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, NY 10021, USA.
J Clin Oncol. 2012 Mar 20;30(9):1005-14. doi: 10.1200/JCO.2010.31.8907. Epub 2012 Feb 21.
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.
Janus 激酶/信号转导和转录激活因子（Jak/Stat）通路是 20 年前作为细胞因子信号转导的介质被发现的。自那时以来，已经发表了超过 2500 篇文章，证明了该通路在几乎所有恶性肿瘤中的重要性。尽管有数十种细胞因子和细胞因子受体、四种 Jak 和七种 Stat，但似乎白细胞介素-6 介导的 Stat3 激活是促进肿瘤发生的主要途径。该转录因子调节肿瘤形成和转移进展的许多关键介质的表达。本综述将探讨该通路在非恶性疾病以及恶性肿瘤（包括肿瘤内在和外在）中的相对重要性和功能、其他 Stat 的影响、该通路抑制剂的开发以及抑制剂在控制或根除癌症中的潜在作用。
