Related Experiment Video
Updated: Dec 12, 2025

Combined Conditional Knockdown and Adapted Sphere Formation Assay to Study a Stemness-Associated Gene of Patient-derived Gastric Cancer Stem Cells
Published on: May 9, 2020
cGAS-STING pathway in oncogenesis and cancer therapeutics
Brandon Yi Da Hoong1,2,3, Yunn Hwen Gan1,2,4, Haiyan Liu2,5
1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Abstract:
The host innate immunity offers the first line of defense against infection. However, recent evidence shows that the host innate immunity is also critical in sensing the presence of cytoplasmic DNA derived from genomic instability events, such as DNA damage and defective cell cycle progression. This is achieved through the cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon (IFN) genes (STING) pathway. Here we discuss recent insights into the regulation of this pathway in cancer immunosurveillance, and the downstream signaling cascades that coordinate immune cell recruitment to the tumor microenvironment to destroy transformed cells through cellular senescence or cell death programs. Its central role in immunosurveillance positions the cGAS-STING pathway as an attractive anti-cancer immunotherapeutic drug target for chemical agonists or vaccine adjuvants and suggests a key node to be targeted in a synthetic lethal approach. We also discuss adaptive mechanisms used by cancer cells to circumvent cGAS-STING signaling and present evidence linking chronic cGAS-STING activation to inflammation-induced carcinogenesis, cautioning against the use of activating the cGAS-STING pathway as an anti-tumor immunotherapy. A deeper mechanistic understanding of the cGAS-STING pathway will aid in the identification of potentially efficacious anti-cancer therapeutic targets.
Insights
The cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon (IFN) genes (STING) pathway detects DNA damage, aiding cancer immunosurveillance. Understanding this pathway offers new therapeutic targets but requires caution due to potential links to carcinogenesis.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Innate immunity acts as the first defense against pathogens.
- The cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon (IFN) genes (STING) pathway senses cytoplasmic DNA from genomic instability.
- This pathway is crucial for detecting DNA damage and cell cycle defects.
Purpose of the Study:
- To review recent findings on cGAS-STING pathway regulation in cancer immunosurveillance.
- To explore downstream signaling in immune cell recruitment and tumor destruction.
- To discuss the cGAS-STING pathway as a therapeutic target and potential risks.
Main Methods:
- Literature review of recent insights into cGAS-STING pathway regulation.
- Analysis of downstream signaling cascades in the tumor microenvironment.
- Discussion of cancer cell evasion mechanisms and chronic activation effects.
Main Results:
- The cGAS-STING pathway mediates cancer immunosurveillance by promoting cellular senescence or death.
- It recruits immune cells to the tumor microenvironment.
- Cancer cells develop adaptive mechanisms to evade cGAS-STING signaling.
Conclusions:
- The cGAS-STING pathway is a promising target for anti-cancer immunotherapies, such as agonists or vaccine adjuvants.
- Targeting cGAS-STING in synthetic lethality approaches is suggested.
- Chronic cGAS-STING activation may promote inflammation-induced carcinogenesis, necessitating careful therapeutic application.
More Related Videos
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Targeted Cancer Therapies
There are several types of targeted therapies against...
Amplifying Signals via Enzymatic Cascade
GPCRs Regulate Adenylyl Cylase Activity
Intracellular Signaling Cascades
mTOR Signaling and Cancer Progression
The mTOR pathway or the...

