Unveiling the crossroads of STING signaling pathway and metabolic reprogramming - the multifaceted role of the STING in the TME and new prospects in cancer therapies

Sep 23, 2026

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The cGAS-STING signaling pathway links DNA sensing to innate immunity and has strong potential to enhance anti-tumor immunity by inducing type I interferons. Despite this promise, STING agonists have shown reduced biotherapeutic efficacy in clinical trials. Tumor metabolism, driven by aberrant nutrient use and energy generation, is a core hallmark of tumorigenesis and offers a therapeutic entry point. Emerging evidence indicates STING also shapes metabolic reprogramming outside its immune role, making metabolic targets relevant for STING activation. This review examines how STING intersects with multiple metabolic pathways, summarizes STING’s antitumor functions, and highlights metabolic targets in the tumor microenvironment (TME) that could be exploited. It emphasizes the need to define STING–metabolism interactions across cancer types and supports personalized strategies based on metabolic profiling.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

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Abstract

Introduction

Wang et al. Cell Communication and Signaling (2025) 23:171 [https://doi.org/10.1186/s12964-025-02169-0](https://doi.org/10.1186/s12964-025-02169-0) Cell Communication and Signaling REVIEW Open Access Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in theTMEand new prospects in cancer therapies Siwei Wang1,2,3†, Lu Qin4,5†, Furong Liu1,2,3* and Zhanguo Zhang1,2,3* Abstract The cGAS-STING signaling pathway serves as a critical link between DNA sensing and innate immunity, and has tremendous potential to improve anti-tumor immunity by generating type I interferons. However, STING agonistshave shown decreasing biotherapeutic efficacy in clinical trials. Tumor metabolism, characterized by aberrant nutrient utilization and energy production, is a fundamental hallmark of tumorigenesis. And modulating metabolic pathways in tumor cells has been discovered as a therapeutic strategy for tumors. As research concerning STING progressed, emerging evidence highlights its role in metabolic reprogramming, independent its immune function, indicating metabolic targets as a strategy for STING activation in cancers. In this review, we delve into the interplay between STING and multiple metabolic pathways. We also synthesize current knowledge on the antitumor functions of STING, and the metabolic targets within the tumor microenvironment (TME) that could be exploited for STING activation. This review highlights the necessity for future research to dissect the complex metabolic interactions with STING in various cancer types, emphasizing the potential for personalized therapeutic strategies based on metabolic profiling. †Siwei Wang and Lu Qin contributed equally to this work. *Correspondence: Furong Liu [liufurong@tjh.tjmu.edu.cn](liufurong@tjh.tjmu.edu.cn)[ ](liufurong@tjh.tjmu.edu.cn)Zhanguo Zhang [zhanguo_tjh@hust.edu.cn](zhanguo_tjh@hust.edu.cn) 1 Hepatic Surgery Center, Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, Hubei, China 2 Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, Hubei, China 3 Present Address: Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China 4 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 5 Present Address: Key Laboratory of Anesthesiology and Resuscitation, Ministry of Education, Huazhong University of Science and Technology), Wuhan, China © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.) Wang et al. Cell Communication and Signalin

FAQs

What is the role of the cGAS-STING pathway in anti-tumor immunity?

It links DNA sensing to innate immunity and can promote anti-tumor responses by generating type I interferons.

Why have STING agonists shown decreasing efficacy in clinical trials?

The document notes that clinical efficacy has declined, and it frames tumor metabolism and the need for metabolic targeting as part of the broader context for STING activation strategies.

How does STING relate to tumor metabolism and metabolic reprogramming?

The review highlights evidence that STING participates in metabolic reprogramming, affecting pathways such as glycolysis and lipid-related processes, independently of its immune functions.

Sep 23, 2026

Uploaded by Aurelia