Abstract
Recent studies have shown that genomic instability in tumor cells leads to activation of inflammatory signaling through the cGAS/STING pathway. In this review, we describe multiple ways by which genomic instability leads to cGAS/STING-mediated inflammatory signaling, as well as the consequences for tumor development and the tumor microenvironment. Also, we elaborate on how tumor cells have apparently evolved to escape the immune surveillance mechanisms that are triggered by cGAS/STING signaling. Finally, we describe how cGAS/STING-mediated inflammatory signaling can be therapeutically targeted to improve therapy responses.
Keywords:
Genomic instability; STING; cGAS; cytoplasmic DNA; inflammatory signaling; interferon response.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cytosol / metabolism
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DNA Damage / genetics
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DNA Repair / genetics
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DNA, Single-Stranded / genetics
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DNA, Single-Stranded / metabolism
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Genomic Instability*
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Humans
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Immunotherapy / methods
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Inflammation / metabolism
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Membrane Proteins / metabolism
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Molecular Targeted Therapy / methods
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Neoplasms / drug therapy
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Neoplasms / genetics*
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Neoplasms / metabolism*
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Nucleotidyltransferases / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics*
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Tumor Escape / genetics
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Tumor Microenvironment / genetics
Substances
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DNA, Single-Stranded
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Membrane Proteins
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STING1 protein, human
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Nucleotidyltransferases
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cGAS protein, human
Grants and funding
This work was supported by the European Research Council [ERC CoS Grant 682421]; Dutch Cancer Society/Alpe d’HuZes [EMCR2014-7048].