Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.
尽管我们对肿瘤发生的分子机制理解已取得进展，癌症仍是导致死亡的主要原因。癌细胞的恶性行为主要由转录因子的异常激活驱动。特别是信号转导与转录激活因子（STATs），它们调控着增殖、凋亡和分化等许多关键细胞过程，在多种人类癌症中常被异常激活。多条信号通路汇聚于STATs，突显了它们在肿瘤发生发展中的重要性。STAT3和STAT5是STAT蛋白家族中最常在癌症中被激活的两个成员，可直接驱动癌症发病机制。过去十年间，针对STAT3和STAT5抑制剂的研发已成为研究热点，尽管有效的治疗选择仍然有限。本综述探讨了STAT3和STAT5在正常生理和癌症生物学中的具体作用，讨论了药物靶向STAT蛋白及其上游激活因子的机遇与挑战，并对识别STAT抑制剂作为癌症治疗新策略提出了见解。
肿瘤(癌症)患者之家