癌症中针对STING的靶向作用：挑战与新兴机遇。
Targeting STING in cancer: Challenges and emerging opportunities.
发表日期：2023 Sep 15
作者：
Kexin Zhao, Jiaojiao Huang, Yue Zhao, Shengjun Wang, Juan Xu, Kai Yin
来源：
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
摘要：
环状鸟苷酸-磷酸二酯酶（cGAS）-干扰素基因刺激因子（STING）信号通路是机体通过识别异常来源的细胞质双链DNA来调节免疫反应的关键通路，并在肿瘤生长和转移中起重要作用，相关分子细节不断被探索和更新。STING具有显著的免疫调节作用，使其成为肿瘤免疫治疗的有吸引力的靶点，STING激动剂因其开发和临床转化而受到极大关注。尽管在临床前研究中取得了令人振奋的结果，但由于其药代动力学和理化性质较差以及产生的毒性副作用，STING激动剂在癌症治疗中的应用仍然具有挑战性。在这里，我们总结了cGAS-STING在癌症中的两面角色，并讨论了基于STING激活的癌症免疫治疗的限制，以及克服这些限制实现肿瘤消退的可行策略。版权所有©2023 Elsevier公司。保留所有权利。
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a key pathway through which the host regulates immune responses by recognizing cytoplasmic double-stranded DNA of abnormal origin, and it plays an important role in tumor growth as well as metastasis, with relevant molecular details constantly being explored and updated. The significant immunomodulatory effects make STING an attractive target for cancer immunotherapy, and STING agonists have been receiving great attention for their development and clinical translation. Despite exciting results in preclinical work, the application of STING agonists to cancer therapy remains challenging due to their poor pharmacokinetic and physicochemical properties, as well as toxic side effects they produce. Here, we summarize the dichotomous role of cGAS-STING in cancer and discuss the limitations of cancer immunotherapy based on STING activation as well as feasible strategies to overcome them to achieve tumor regression.Copyright © 2023 Elsevier B.V. All rights reserved.