Arshad Sundas, Naveed Muhammad, Ullia Mahad, Javed Khadija, Butt Ayesha, Khawar Masooma, Amjad Fazeeha
University of Lahore, Department of Allied Health Sciences, Gujrat Campus, Pakistan.
University of Central Punjab, Faculty of life sciences, Department of Biotechnology, Lahore, Pakistan.
Genet Mol Biol. 2020 Feb 10;43(1):e20180160. doi: 10.1590/1678-4685-GMB-2018-0160. eCollection 2020.
Signal transducers and activators of transcription 3 (STAT-3) is a transcription factor that regulates the gene expression of several target genes. These factors are activated by the binding of cytokines and growth factors with STAT-3 specific receptors on cell membrane. Few years ago, STAT-3 was considered an acute phase response element having several cellular functions such as inflammation, cell survival, invasion, metastasis and proliferation, genetic alteration, and angiogenesis. STAT-3 is activated by several types of inflammatory cytokines, carcinogens, viruses, growth factors, and oncogenes. Thus, the STAT3 pathway is a potential target for cancer therapeutics. Abnormal STAT-3 activity in tumor development and cellular transformation can be targeted by several genomic and pharmacological methodologies. An extensive review of the literature has been conducted to emphasize the role of STAT-3 as a unique cancer drug target. This review article discusses in detail the wide range of STAT-3 inhibitors that show antitumor effects both in vitro and in vivo. Thus, targeting constitutive STAT-3 signaling is a remarkable therapeutic methodology for tumor progression. Finally, current limitations, trials and future perspectives of STAT-3 inhibitors are also critically discussed.
信号转导与转录激活因子3（STAT-3）是一种转录因子，可调节多个靶基因的基因表达。这些因子通过细胞因子和生长因子与细胞膜上的STAT-3特异性受体结合而被激活。几年前，STAT-3被认为是一种急性期反应元件，具有多种细胞功能，如炎症、细胞存活、侵袭、转移和增殖、基因改变以及血管生成。STAT-3可被多种类型的炎性细胞因子、致癌物、病毒、生长因子和癌基因激活。因此，STAT3信号通路是癌症治疗的一个潜在靶点。肿瘤发展和细胞转化过程中异常的STAT-3活性可通过多种基因组学和药理学方法进行靶向干预。我们进行了广泛的文献综述，以强调STAT-3作为一种独特的癌症药物靶点的作用。这篇综述文章详细讨论了多种在体外和体内均显示出抗肿瘤作用的STAT-3抑制剂。因此，靶向组成型STAT-3信号传导是一种针对肿瘤进展的显著治疗方法。最后，还对STAT-3抑制剂目前的局限性、试验情况及未来前景进行了批判性讨论。
