Xuan Chenyuan, Hu Rong
Department of Pharmacology, China Pharmaceutical University, No 24, TongJiaXiang, Gulou District, Nanjing, 210009, P. R. China.
ChemMedChem. 2023 Dec 1;18(23):e202300405. doi: 10.1002/cmdc.202300405. Epub 2023 Oct 20.
Stimulator of interferon genes (STING) is a crucial adaptor protein in the innate immune response. STING activation triggers cytokine secretion, including type I interferon and initiates T cell-mediated adaptive immunity. The activated immune system converts "cold tumors" into "hot tumors" that are highly responsive to T cells by recruiting them to the tumor microenvironment, ultimately leading to potent and long-lasting antitumor effects. Unlike most immune checkpoint inhibitors, STING agonists represent a groundbreaking class of innate immune agonists that hold great potential for effectively targeting various cancer populations and are poised to become a blockbuster in tumor immunotherapy. This review will focus on the correlation between the STING signaling pathway and tumor immunity, as well as explore the impact of STING activation on other biological processes. Ultimately, we will summarize the development and optimization of STING agonists from a medicinal chemistry perspective, evaluate their potential in cancer therapy, and identify possible challenges for future advancement.
干扰素基因刺激因子（STING）是先天性免疫反应中一种关键的衔接蛋白。STING激活会触发细胞因子分泌，包括I型干扰素，并启动T细胞介导的适应性免疫。激活的免疫系统通过将T细胞招募到肿瘤微环境中，将“冷肿瘤”转化为对T细胞高度敏感的“热肿瘤”，最终产生强大而持久的抗肿瘤作用。与大多数免疫检查点抑制剂不同，STING激动剂代表了一类开创性的先天性免疫激动剂，在有效靶向各种癌症群体方面具有巨大潜力，有望成为肿瘤免疫治疗中的重磅药物。本综述将聚焦于STING信号通路与肿瘤免疫之间的相关性，并探讨STING激活对其他生物学过程的影响。最终，我们将从药物化学角度总结STING激动剂的研发与优化，评估其在癌症治疗中的潜力，并确定未来进展可能面临的挑战。
