Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, New York, NY, USA.
Nat Rev Drug Discov. 2019 Nov;18(11):845-867. doi: 10.1038/s41573-019-0043-2. Epub 2019 Sep 25.
Nucleic acid sensors, primarily TLR and RLR family members, as well as cGAS-STING signalling, play a critical role in the preservation of cellular and organismal homeostasis. Accordingly, deregulated nucleic acid sensing contributes to the origin of a diverse range of disorders, including infectious diseases, as well as cardiovascular, autoimmune and neoplastic conditions. Accumulating evidence indicates that normalizing aberrant nucleic acid sensing can mediate robust therapeutic effects. However, targeting nucleic acid sensors with pharmacological agents, such as STING agonists, presents multiple obstacles, including drug-, target-, disease- and host-related issues. Here, we discuss preclinical and clinical data supporting the potential of this therapeutic paradigm and highlight key limitations and possible strategies to overcome them.
核酸传感器，主要是 TLR 和 RLR 家族成员，以及 cGAS-STING 信号通路，在维持细胞和机体的内稳态方面发挥着关键作用。因此，核酸传感失调会导致多种疾病的发生，包括传染病以及心血管、自身免疫和肿瘤疾病。越来越多的证据表明，规范异常的核酸传感可以介导强大的治疗效果。然而，使用药理学药物（如 STING 激动剂）靶向核酸传感器存在多种障碍，包括药物、靶标、疾病和宿主相关问题。在这里，我们讨论了支持这种治疗模式潜力的临床前和临床数据，并强调了克服这些限制的关键策略。
