Sarcoma Research Group, Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales, Randwick, NSW, Australia.
Int J Oncol. 2012 Oct;41(4):1181-91. doi: 10.3892/ijo.2012.1568. Epub 2012 Jul 24.
Signal transducer and activator of transcription 3 (STAT3) regulates many critical functions in human normal and malignant tissues, such as differentiation, proliferation, survival, angiogenesis and immune function. Constitutive activation of STAT3 is implicated in a wide range of human cancers. As such, STAT3 has been studied as a tumour therapeutic target. This review aimed principally to summarise the updated research on STAT3 inhibition studies and their therapeutic potential in solid tumours. Recent literature associated with STAT3 inhibition was reviewed through PubMed and Medline database, followed by critical comparison and analysis. Constitutive activation of STAT3 has been identified as abnormal and oncogenic. The pathway of STAT3 activation and signal transduction identifies 3 approaches for inhibition: modulating upstream positive or negative regulators, regulating RNA (DN-STAT3, anti-sense RNA, siRNA and microRNA) or targeting STAT3 protein at different domains. The last approach using small molecule STAT3 inhibitors has been the most examined so far with both preclinical and clinical studies. Targeting STAT3 using a specific inhibitor may be a useful cancer treatment approach, with the potential for a broad clinical impact.
信号转导子和转录激活子 3（STAT3）调节人类正常和恶性组织中的许多关键功能，如分化、增殖、存活、血管生成和免疫功能。STAT3 的组成性激活与广泛的人类癌症有关。因此，STAT3 已被研究为肿瘤治疗靶点。本综述旨在主要总结 STAT3 抑制研究的最新研究及其在实体瘤中的治疗潜力。通过 PubMed 和 Medline 数据库回顾了与 STAT3 抑制相关的最新文献，并进行了批判性比较和分析。STAT3 的组成性激活被认为是异常和致癌的。STAT3 激活和信号转导途径确定了 3 种抑制方法：调节上游正或负调节剂、调节 RNA（DN-STAT3、反义 RNA、siRNA 和 microRNA）或在不同结构域靶向 STAT3 蛋白。迄今为止，使用小分子 STAT3 抑制剂的最后一种方法已经进行了最广泛的临床前和临床研究。使用特异性抑制剂靶向 STAT3 可能是一种有用的癌症治疗方法，具有广泛的临床影响潜力。
