Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases

Arch Pharm Res. 2023 Jun;46(6):500-534. doi: 10.1007/s12272-023-01452-3. Epub 2023 Jun 24.

Abstract

Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a DNA sensor that elicits a robust type I interferon response by recognizing ubiquitous danger-associated molecules. The cGAS/stimulator of interferon genes (cGAS/STING) is activated by endogenous DNA, including DNA released from mitochondria and extranuclear chromatin, as well as exogenous DNA derived from pathogenic microorganisms. cGAS/STING is positioned as a key axis of autoimmunity, the inflammatory response, and cancer progression, suggesting that the cGAS/STING signaling pathway represents an efficient therapeutic target. Based on the accumulated evidence, we present insights into the prevention and treatment of cGAS/STING-related chronic immune and inflammatory diseases. This review presents the current state of clinical and nonclinical development of modulators targeting cGAS/STING, providing useful information on the design of therapeutic strategies.

Keywords: Cancer; DNA, immunity; Inflammation; STING; cGAS.

Publication types

  • Review

MeSH terms

  • DNA
  • Humans
  • Immunity, Innate
  • Interferon Type I* / genetics
  • Interferon Type I* / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / metabolism
  • Signal Transduction / physiology

Substances

  • Nucleotidyltransferases
  • DNA
  • Interferon Type I