Wang Han-Qi, Man Qi-Wen, Huo Fang-Yi, Gao Xin, Lin Hao, Li Su-Ran, Wang Jing, Su Fu-Chuan, Cai Lulu, Shi Yi, Liu Bing, Bu Lin-Lin
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education School & Hospital of Stomatology Wuhan University Wuhan China.
Department of Oral & Maxillofacial Head Neck Oncology School & Hospital of Stomatology Wuhan University Wuhan China.
MedComm (2020). 2022 Mar 23;3(2):e124. doi: 10.1002/mco2.124. eCollection 2022 Jun.
Signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, discovered in the cytoplasm of almost all types of mammalian cells, plays a significant role in biological functions. The duration of STAT3 activation in normal tissues is a transient event and is strictly regulated. However, in cancer tissues, STAT3 is activated in an aberrant manner and is induced by certain cytokines. The continuous activation of STAT3 regulates the expression of downstream proteins associated with the formation, progression, and metastasis of cancers. Thus, elucidating the mechanisms of STAT3 regulation and designing inhibitors targeting the STAT3 pathway are considered promising strategies for cancer treatment. This review aims to introduce the history, research advances, and prospects concerning the STAT3 pathway in cancer. We review the mechanisms of STAT3 pathway regulation and the consequent cancer hallmarks associated with tumor biology that are induced by the STAT3 pathway. Moreover, we summarize the emerging development of inhibitors that target the STAT3 pathway and novel drug delivery systems for delivering these inhibitors. The barriers against targeting the STAT3 pathway, the focus of future research on promising targets in the STAT3 pathway, and our perspective on the overall utility of STAT3 pathway inhibitors in cancer treatment are also discussed.
信号转导和转录激活因子3（STAT3）是STAT家族的成员之一，在几乎所有类型的哺乳动物细胞的细胞质中被发现，在生物学功能中发挥着重要作用。STAT3在正常组织中的激活持续时间是一个短暂的事件，并且受到严格调控。然而，在癌组织中，STAT3以异常的方式被激活，并由某些细胞因子诱导。STAT3的持续激活调节与癌症的形成、进展和转移相关的下游蛋白的表达。因此，阐明STAT3的调控机制并设计靶向STAT3途径的抑制剂被认为是癌症治疗的有前景的策略。本综述旨在介绍癌症中STAT3途径的历史、研究进展和前景。我们综述了STAT3途径调控的机制以及由STAT3途径诱导的与肿瘤生物学相关的癌症特征。此外，我们总结了靶向STAT3途径的抑制剂以及用于递送这些抑制剂的新型药物递送系统的新进展。还讨论了靶向STAT3途径的障碍、STAT3途径中有前景的靶点的未来研究重点以及我们对STAT3途径抑制剂在癌症治疗中的整体效用的看法。
