Opportunities and challenges of targeting cGAS-STING in cancer
Changzheng Lu1, Wenyan Wang2, Yang-Xin Fu3
1Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China. changzheng.lu@szbl.ac.cn.
Abstract:
The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway has a crucial role in detecting tumour-derived DNA, whether the pathway is generated spontaneously or induced therapeutically. Activation of the cGAS-STING pathway triggers type I interferon signalling and pro-inflammatory responses in both tumour and immune cells, establishing a delicate balance between pathological inflammation and protective immune responses. Although preclinical studies have highlighted the promise of targeting the cGAS-STING pathway to enhance antitumour immunotherapy, clinical results have fallen short of expectations. In this Review, we outline key advances in understanding the tumour-promoting and tumour-suppressive effects mediated by the cGAS-STING pathway and discuss opportunities and challenges for its integration into future cancer immunotherapy.
Insights
The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway detects tumor DNA, influencing cancer immunity. Despite promise, clinical applications of targeting this pathway for cancer immunotherapy face challenges.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for sensing tumor DNA.
- This pathway activates type I interferon signaling and inflammatory responses, impacting the tumor microenvironment.
Purpose of the Study:
- To review advances in understanding the dual role of the cGAS-STING pathway in cancer.
- To discuss the potential and challenges of targeting this pathway for cancer immunotherapy.
Main Methods:
- Literature review of preclinical and clinical studies on the cGAS-STING pathway in cancer.
- Analysis of mechanisms underlying tumor promotion and suppression by cGAS-STING.
Main Results:
- Preclinical studies show promise for cGAS-STING targeting in immunotherapy.
- Clinical outcomes have not met expectations, indicating a complex role in cancer.
Conclusions:
- The cGAS-STING pathway presents both tumor-promoting and tumor-suppressive effects.
- Further research is needed to overcome challenges and effectively integrate cGAS-STING targeting into cancer immunotherapy strategies.
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