cGAS-STING signaling - a therapeutic target in inflammatory bowel disease and related colorectal cancer

Sep 22, 2026

cGAS-STING signaling is a key innate immune DNA-sensing mechanism that can drive interferon and pro-inflammatory cytokine production. In the intestine, it supports bidirectional regulation: properly activated signaling helps maintain homeostasis and suppress tumorigenesis, whereas excessive activation promotes inflammatory responses. This review consolidates recent molecular insights into cGAS-STING regulatory functions in colorectal tumors and inflammatory bowel disease and examines pathway-targeting therapeutic strategies for intestinal disease treatment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Introduction

The signaling pathway of cGASSTING

DNA sensing by cGAS

TYPE Review PUBLISHED 15 January 2026 DOI 10.3389/fimmu.2025.1709908 OPEN ACCESS EDITED BY Steven O'Reilly, Consultant, Sunderland, United Kingdom REVIEWED BY Milad khorasani, Neyshabur University of Medical Sciences, Iran Valerie Quesniaux, UMR7355 Immunologie et Neuroge´ne´tique Expe´rimentales et Mole´culaires (INEM), France *CORRESPONDENCE Fei Mao [maofei2003@ujs.edu.cn](maofei2003@ujs.edu.cn) †These authors have contributed equally to this work RECEIVED 26 September 2025 REVISED 19 December 2025 ACCEPTED 24 December 2025 PUBLISHED 15 January 2026 CITATION Chen X, Tang X, Chen S, Ye Y and Mao F (2026) cGAS-STING signaling: a therapeutic target in inﬂammatory bowel disease and related colorectal cancer. Front. Immunol. 16:1709908 . doi: 10.3389/fimmu.2025.1709908 COPYRIGHT © 2026 Chen, Tang, Chen, Ye and Mao. This isan open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. cGAS-STING signaling: a therapeutic target in inﬂammatory bowel disease and related colorectal cancer Xi Chen 1,2†, Xiaohua Tang 3†, Sixuan Chen 1,2, Yang Ye 1 and Fei Mao 1,2* 1 Department of laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China, 2 Department of Laboratory Medicine, the Afﬁliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China, 3The People’s Hospital of Danyang, Afﬁliated Danyang Hospital of Nantong University, Jiangsu University, Zhenjiang, Jiangsu, China The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a critical mechanism of DNA sensing in innate immunity. Activation of this pathway can induce the production of interferons and proinﬂammatory cytokines. In the intestine, this pathway exhibits bidirectional regulatory properties, with appropriate activation maintaining homeostasis and inhibiting tumorigenesis, while excessive activation leads to inﬂammatory responses. A thorough exploration of the molecular mechanisms and regulatory networks of the cGAS-STING signaling pathway offers a signiﬁcant theoretical foundation and potential treatment targets for developing novel strategies to treat intestinal diseases. This review summarizes the most recent developments on the function of the cGAS-STING regulatory pathway in colorectal tumors and inﬂammatory bowel disease. It discusses targeted therapeutic approaches that interfere with this pathway. KEYWORDS CGAS, colorectal cancer, inﬂammatory bowel disease, STING, therapy 1 Introduction The intestinal mucosal immune system is the core regulator of intestinal homeostasis. It achieves adaptive responses to commensal microorganisms and food-borne antigens by precisely balancing immune defense and immune tolerance. Disruption of this immune homeostasis can trigger chronic inﬂammatory responses and increase the risk of tumorigenesis (1–3) . In recent years, the role of the innate immune system in the pathogenesis of intestinal diseases has attracted considerable attention. Among them, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, as a key pathway for cytoplasmic DNA sensing, plays an important regulatory role in infection, inﬂammation, and tumorigenesis (4, 5) . cGAS is a key molecule in cytoplasmic DNA sensing that can speciﬁcally recognize exogenous pathogens (such as Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) viruses and bacteria) and endogenous damage-related (such as mitochondrial and nuclear sources) double-stranded DNA (dsDNA) (5, 6) . Upon activation, it catalyzes the synthesis of 2'

FAQs

What does cGAS-STING signaling do in innate immunity?

It is a DNA-sensing pathway that, once activated, promotes production of type I interferons and pro-inflammatory cytokines through downstream signaling cascades.

How is cGAS-STING signaling regulated in the intestine?

It shows bidirectional regulatory effects: appropriate activation supports intestinal homeostasis and inhibits tumorigenesis, while excessive activation triggers inflammatory responses.

What therapeutic approaches does the review focus on?

The review summarizes targeted strategies that interfere with the cGAS-STING signaling pathway to address colorectal cancer and inflammatory bowel disease.

Sep 22, 2026

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