The cGAS-STING pathway as a novel therapeutic strategy for pancreatic diseases

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2024-12, Vol.184, p.156801, Article 156801
• Main Authors: Pei, Zhengda, Tian, Mengxiang
• Format: Article
• Language: English
• Subjects: Acute pancreatitis; cGAS-STING; Chronic pancreatitis; Pancreatic cancer; Pancreatic diseases; Therapeutic potential
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2024.156801

•Overactivation of the cGAS-STING pathway worsens acute pancreatitis but can reduce fibrosis and islet damage in chronic cases.•Activating the cGAS-STING pathway can facilitate the treatment of pancreatic cancer.•Several cGAS-STING inhibitors and activators are in clinical trials. The Cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes [1] signaling pathway has emerged as a pivotal immune response mechanism, activating immune defenses upon detection of both exogenous and endogenous DNA within cells. Its activation is intricately linked to various diseases and inflammatory processes, spanning autoimmune disorders, infectious ailments, and malignancies. Among pancreatic diseases, encompassing acute pancreatitis, chronic pancreatitis, and pancreatic cancer, current clinical treatment efficacy remains suboptimal. Here, we elucidate the molecular intricacies of the cGAS-STING signaling pathway and delineate its therapeutic potential in acute pancreatitis, chronic pancreatitis, and pancreatic cancer. Additionally, we offer an overview of recent advancements in STING agonists and antagonists, assessing their therapeutic potential in pancreatic-related disorders. In summary, by exploring the multifaceted roles of the cGAS-STING signaling pathway and its implications in pancreatic diseases, we aim to shed light on potential avenues for therapeutic intervention and management in these challenging clinical contexts.