School of Basic Medical Sciences, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
PeerJ. 2024 Nov 22;12:e18559. doi: 10.7717/peerj.18559. eCollection 2024.
Lung cancer (LC) remains one of the most prevalent and lethal malignancies globally, with a 5-year survival rate for advanced cases persistently below 10%. Despite the significant advancements in immunotherapy, a substantial proportion of patients with advanced LC fail to respond effectively to these treatments, highlighting an urgent need for novel immunotherapeutic targets. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has gained prominence as a potential target for improving LC immunotherapy due to its pivotal role in enhancing anti-tumor immune responses, augmenting tumor antigen presentation, and promoting T cell infiltration. However, emerging evidence also suggests that the cGAS-STING pathway may have pro-tumorigenic effects in the context of LC. This review aims to provide a comprehensive analysis of the cGAS-STING pathway, including its biological composition, activation mechanisms, and physiological functions, as well as its dual roles in LC and the current and emerging LC treatment strategies that target the pathway. By addressing these aspects, we intend to highlight the potential of the cGAS-STING pathway as a novel immunotherapeutic target, while also considering the challenges and future directions for its clinical application.
肺癌（LC）仍然是全球最普遍和最致命的恶性肿瘤之一，晚期病例的 5 年生存率持续低于 10%。尽管免疫疗法取得了重大进展，但相当一部分晚期 LC 患者对这些治疗反应不佳，这突显了对新型免疫治疗靶点的迫切需求。环鸟苷酸-腺苷酸合成酶（cGAS）-干扰素基因刺激物（STING）途径由于其在增强抗肿瘤免疫反应、增强肿瘤抗原呈递和促进 T 细胞浸润方面的关键作用，已成为改善 LC 免疫治疗的潜在靶点。然而，新出现的证据也表明，cGAS-STING 途径在 LC 中可能具有促肿瘤作用。本综述旨在全面分析 cGAS-STING 途径，包括其生物学组成、激活机制和生理功能，以及其在 LC 中的双重作用以及目前和新兴的针对该途径的 LC 治疗策略。通过解决这些方面，我们旨在强调 cGAS-STING 途径作为一种新型免疫治疗靶点的潜力，同时考虑其临床应用的挑战和未来方向。
