Papadakos Stavros P, Georgiadou Chara, Argyrou Alexandra, Michailidou Elisavet, Thanos Charalampos, Vogli Stamatina, Siakavellas Spyros I, Manolakopoulos Spillios, Theocharis Stamatios
First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
1st Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 11527 Athens, Greece.
Int J Mol Sci. 2025 May 22;26(11):4979. doi: 10.3390/ijms26114979.
Inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) remains a significant clinical challenge due to its link with chronic inflammation and the inherent limitations of current prevention and surveillance strategies. The cGAS-STING pathway has emerged as a key player in the immune regulation of inflammation-driven carcinogenesis, demonstrating both protective and pathogenic roles. This review examines the contrasting roles of the cGAS-STING signaling pathway in intestinal inflammation and colitis-associated cancer (CAC), emphasizing its promise as a target for cancer prevention strategies. Evidence suggests that modulating this pathway could preserve epithelial integrity, limit chronic inflammation, and bolster anti-tumor immunity. Despite advancements in therapies like mesalazine and surveillance colonoscopy programs, gaps in efficacy remain, particularly for Crohn's disease and high-risk populations. Future research should focus on integrating cGAS-STING-targeted approaches with existing modalities to provide personalized and less invasive strategies for CAC prevention. By harnessing this pathway's therapeutic potential, a paradigm shift in managing IBD-associated CRC may be achieved, addressing the challenges of long-term disease surveillance and prevention.
炎症性肠病（IBD）相关的结直肠癌（CRC）仍然是一个重大的临床挑战，因为它与慢性炎症有关，且当前的预防和监测策略存在固有局限性。环鸟苷酸-腺苷酸合成酶（cGAS）-干扰素基因刺激蛋白（STING）通路已成为炎症驱动的致癌作用免疫调节中的关键参与者，显示出保护和致病双重作用。本综述探讨了cGAS-STING信号通路在肠道炎症和结肠炎相关癌症（CAC）中的不同作用，强调了其作为癌症预防策略靶点的前景。有证据表明，调节该通路可维持上皮完整性、限制慢性炎症并增强抗肿瘤免疫力。尽管美沙拉嗪等疗法以及监测结肠镜检查项目取得了进展，但疗效仍存在差距，尤其是对于克罗恩病和高危人群。未来的研究应专注于将针对cGAS-STING的方法与现有模式相结合，以提供个性化且侵入性较小的CAC预防策略。通过利用该通路的治疗潜力，或许可以实现IBD相关CRC管理的范式转变，应对长期疾病监测和预防的挑战。
