Role of the cGAS–STING pathway in cancer development and oncotherapeutic approaches

The cyclic GMP‐AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway mediates anti‐microbial innate immunity by inducing the production of type I interferons (IFNs) and inflammatory cytokines upon recognition of microbial DNA. Recent studies reveal that self‐DNA from tumors and by‐produ...

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Bibliographic Details
Published in:EMBO reports 2018-12, Vol.19 (12), p.n/a
Main Authors: Khoo, Li Teng, Chen, Liuh‐Yow
Format: Article
Language:English
Subjects:
AMP
Animals
Cancer
Carcinogenesis - metabolism
Carcinogenesis - pathology
cGAS
Cyclic GMP
Cytokines
Deoxyribonucleic acid
DNA
Drug development
EMBO03
EMBO19
Genomic instability
Humans
Immune checkpoint
immune therapy
Immunity
Inflammation
Innate immunity
Interferon
Membrane Proteins - metabolism
Microorganisms
Neoplasms - therapy
Nucleotidyltransferases - metabolism
Oncolysis
oncolytic virus
Review
Reviews
Signal Transduction
Stability
Stimulators
STING
Telomere - metabolism
Tumors
Viruses
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Summary:The cyclic GMP‐AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway mediates anti‐microbial innate immunity by inducing the production of type I interferons (IFNs) and inflammatory cytokines upon recognition of microbial DNA. Recent studies reveal that self‐DNA from tumors and by‐products of genomic instability also activates the cGAS–STING pathway and either promotes or inhibits tumor development. This has led to the development of cancer therapeutics using STING agonists alone and in combination with conventional cancer treatment or immune checkpoint targeting. On the other hand, for cancers lacking the cGAS–STING pathway and thus a regular innate immunity response, oncolytic virus therapy has been shown to have therapeutic potential. We here review and discuss the dichotomous roles of the cGAS–STING pathway in cancer development and therapeutic approaches. Graphical Abstract cGAS–STING recognizes microbial and also self‐DNA, e.g. derived from tumors, which either activates or inhibits tumor development. This review discusses the dichotomous roles of the cGAS–STING pathway in cancer development and therapeutic approaches.
ISSN:1469-221X
1469-3178
DOI:10.15252/embr.201846935