Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States; Department of Computer and Information Science, Indiana University Purdue University Indianapolis, Indiana, United States.
Pharmacol Ther. 2018 Nov;191:74-91. doi: 10.1016/j.pharmthera.2018.06.006. Epub 2018 Jun 20.
Signal transducer and activator of transcription 3 (STAT3) controls many biological processes including differentiation, survival, proliferation, and angiogenesis. In normal healthy cells, STAT3 is tightly regulated to maintain a momentary active state. However, aberrant or constitutively activated STAT3 has been observed in many different cancers and constitutively activated STAT3 has been shown to associate with poor prognosis and tumor progression. For this reason, STAT3 has been studied as a possible target in the treatment of many different types of cancers. However, despite decades of research, a FDA-approved STAT3 inhibitor has yet to emerge. In this review, we will analyze past studies targeting STAT3 for drug discovery, understand possible causes of failure in these studies, and provide potential insights for future efforts to overcome these roadblocks.
信号转导和转录激活因子 3（STAT3）控制着许多生物学过程，包括分化、存活、增殖和血管生成。在正常健康细胞中，STAT3 受到严格调控，以保持短暂的激活状态。然而，在许多不同的癌症中观察到异常或组成性激活的 STAT3，并且已经表明组成性激活的 STAT3 与不良预后和肿瘤进展相关。出于这个原因，STAT3 已被研究为治疗许多不同类型癌症的可能靶点。然而，尽管经过了几十年的研究，仍然没有一种 FDA 批准的 STAT3 抑制剂问世。在这篇综述中，我们将分析过去针对 STAT3 的药物发现研究，了解这些研究失败的可能原因，并为未来克服这些障碍提供潜在的见解。
