Signal Transducer and Activator of Transcription 3 (STAT3) plays a significant role in diverse physiologic processes, including cell proliferation, differentiation, angiogenesis, and survival. STAT3 activation via phosphorylation of tyrosine and serine residues is a complex and tightly regulated process initiated by upstream signaling pathways with ligand binding to receptor and non-receptor-linked kinases. Through downstream deregulation of target genes, aberrations in STAT3 activation are implicated in tumorigenesis, metastasis, and recurrence in multiple cancers. While there have been extensive efforts to develop direct and indirect STAT3 inhibitors using novel drugs as a therapeutic strategy, direct clinical application remains in evolution. In this review, we outline the mechanisms of STAT3 activation, the resulting downstream effects in physiologic and malignant settings, and therapeutic strategies for targeting STAT3. We also summarize the pre-clinical and clinical evidence of novel drug therapies targeting STAT3 and discuss the challenges of establishing their therapeutic efficacy in the current clinical landscape.
信号转导与转录激活因子3（STAT3）在多种生理过程中扮演关键角色，包括细胞增殖、分化、血管生成和存活。STAT3通过酪氨酸和丝氨酸残基磷酸化被激活，这一过程复杂且受到严格调控，始于配体与受体及非受体相关激酶结合的上游信号通路。通过对靶基因的下游失调，STAT3激活异常与多种癌症的肿瘤发生、转移和复发密切相关。尽管已投入大量努力开发直接和间接的STAT3抑制剂作为治疗策略，但其直接临床应用仍处于发展阶段。本综述概述了STAT3的激活机制、在生理和恶性环境中的下游效应，以及靶向STAT3的治疗策略。同时，我们总结了靶向STAT3的新型药物疗法的临床前和临床证据，并讨论了在当前临床环境中确立其疗效所面临的挑战。
Exploring Novel Frontiers: Leveraging STAT3 Signaling for Advanced Cancer Therapeutics
肿瘤(癌症)患者之家