Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, PR China.
Mol Cancer. 2020 Sep 4;19(1):136. doi: 10.1186/s12943-020-01247-w.
The activation of the cGAS-STING pathway has tremendous potential to improve anti-tumor immunity by generating type I interferons. In recent decades, we have witnessed that producing dsDNA upon various stimuli is an initiative factor, triggering the cGAS-SING pathway for a defensive host. The understanding of both intracellular cascade reaction and the changes of molecular components gains insight into type I IFNs and adaptive immunity. Based on the immunological study, the STING-cGAS pathway is coupled to cancer biotherapy. The most challenging problem is the limited therapeutic effect. Therefore, people view 5, 6-dimethylxanthenone-4-acetic acid, cyclic dinucleotides and various derivative as cGAS-STING pathway agonists. Even so, these agonists have flaws in decreasing biotherapeutic efficacy. Subsequently, we exploited agonist delivery systems (nanocarriers, microparticles and hydrogels). The article will discuss the activation of the cGAS-STING pathway and underlying mechanisms, with an introduction of cGAS-STING agonists, related clinical trials and agonist delivery systems.
cGAS-STING 通路的激活通过产生 I 型干扰素具有极大的潜力来提高抗肿瘤免疫。近几十年来,我们已经观察到,各种刺激下产生 dsDNA 是一个起始因素,触发 cGAS-SING 通路以进行宿主防御。对细胞内级联反应和分子成分变化的理解深入了解了 I 型 IFNs 和适应性免疫。基于免疫学研究,STING-cGAS 通路与癌症生物治疗相结合。最具挑战性的问题是治疗效果有限。因此,人们将 5,6-二甲基黄嘌呤-4-乙酸、环状二核苷酸及其各种衍生物视为 cGAS-STING 通路激动剂。即便如此,这些激动剂在降低生物治疗效果方面存在缺陷。随后,我们开发了激动剂传递系统(纳米载体、微粒和水凝胶)。本文将讨论 cGAS-STING 通路的激活及其潜在机制,介绍 cGAS-STING 激动剂、相关临床试验和激动剂传递系统。