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）控制许多生物学过程，包括分化，存活，增殖和血管生成。在正常的健康细胞中，STAT3被严格调节以维持瞬时活动状态。然而，已经在许多不同的癌症中观察到异常或组成性活化的STAT3，并且已经证明组成性活化的STAT3与不良的预后和肿瘤进展相关。因此，已经研究了STAT3作为治疗许多不同类型癌症的可能靶标。但是，尽管进行了数十年的研究，但FDA批准的STAT3抑制剂尚未出现。在这篇评论中，我们将分析以往针对STAT3进行药物发现的研究，了解这些研究失败的可能原因，