免疫肿瘤学已成为癌症治疗的革命性策略。通过免疫检查点疗法或嵌合抗原受体 T 细胞进行的基于适应性免疫的治疗干预措施已获得临床批准，可用于各种癌症的单一疗法和联合治疗。尽管这些治疗方法已取得临床成功，但只有少数癌症患者表现出反应，这凸显出迫切需要发现新的治疗分子，以改善临床结果并为下一代免疫疗法铺平道路。鉴于先天免疫系统对抗感染和癌症的关键作用，人们一直致力于开发针对这些途径的新型抗癌疗法。靶向干扰素基因刺激物 (STING) 途径是产生持久抗肿瘤反应的强大策略，并且接头蛋白 STING 的激活会诱导转录级联的启动，从而产生 I 型干扰素、促炎细胞因子和趋化因子。各种 STING 激动剂，包括天然或合成的环状二核苷酸 (CDN) 已被开发为抗癌疗法。然而，由于大多数 CDN 仅限于瘤内给药，因此人们对开发用于全身治疗的非核苷酸激动剂产生了浓厚的兴趣。在这里，我们回顾了 STING 激活疗法在临床前或临床阶段的当前发展。© 2024 Wiley‐VCH GmbH。

Immuno-oncology has become a revolutionary strategy for cancer treatment. Therapeutic interventions based on adaptive immunity through immune checkpoint therapy or chimeric antigen receptor T cells have received clinical approval for monotherapy and combination treatment use in various cancers. Although these treatments have achieved clinical successes, only a minority of cancer patients show a response, highlighting the urgent need to discover new therapeutic molecules that could be exploited to improve clinical outcomes and pave the way for the next generation of immunotherapy. Given the critical role of the innate immune system against infection and cancer, substantial efforts have been dedicated to developing novel anticancer therapeutics that target these pathways. Targeting the stimulator of interferon genes (STING) pathway is a powerful strategy to generate durable antitumor response, and activation of the adaptor protein STING induces the initiation of transcriptional cascades, thereby producing type I interferons, pro-inflammatory cytokines and chemokines. Various STING agonists, including natural or synthetic cyclic dinucleotides (CDNs) have been developed as anticancer therapeutics. However, since most CDNs are confined to intratumoral administration, there has been a great interest in developing non-nucleotide agonists for systemic treatment. Here we review the current development of STING-activating therapeutics in both preclinical or clinical stages.© 2024 Wiley‐VCH GmbH.