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

EMBO Rep. 2018 Dec;19(12):e46935. doi: 10.15252/embr.201846935. Epub 2018 Nov 16.

Abstract

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.

Keywords: STING; cGAS; cancer; immune therapy; oncolytic virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology*
  • Humans
  • Membrane Proteins / metabolism*
  • Neoplasms / therapy*
  • Nucleotidyltransferases / metabolism*
  • Signal Transduction*
  • Telomere / metabolism

Substances

  • Membrane Proteins
  • Nucleotidyltransferases