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Updated: Aug 5, 2026

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
11:44

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo

Published on: September 18, 2014

The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential

Yi Wang1, Juan Angulo-Lozano1,2, Yueqi Wang1,3

  • 1Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, USA.

The Journal of Clinical Investigation
|August 3, 2026
PubMed

Insights

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway plays a dual role in cancer immunity. Acute activation promotes anti-tumor responses, while chronic activation can drive tumor progression and immune suppression.

Area of Science:

  • Innate immunity
  • Cancer immunology
  • DNA sensing

Background:

  • The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway is a crucial innate immune sensor for aberrant DNA.
  • This pathway regulates transcriptional programs linking DNA sensing to immune and stress responses.
  • It is a key regulator of tumor-immune interactions.

Purpose of the Study:

  • To examine how context dictates the consequences of cGAS/STING pathway activation in cancer.
  • To review emerging therapeutic strategies targeting the cGAS/STING pathway.
  • To discuss maximizing the pathway's antitumor potential while minimizing toxicity.

Main Methods:

  • Review of existing literature on cGAS/STING pathway in cancer.
  • Analysis of downstream signaling modules (e.g., type I IFN, NF-κB, autophagy).
  • Examination of spatial and biochemical regulation of cGAS and STING.

Main Results:

  • Acute, compartmentalized cGAS/STING activation promotes anti-tumor immunity (DC cross-priming, cytotoxic lymphocytes).
  • Chronic or dysregulated activation promotes tumor progression, metastasis, and immune dysfunction.
  • Dysregulation leads to suppressive myeloid and B cell populations and lymphocyte dysfunction.

Conclusions:

  • Context-dependent activation of cGAS/STING has opposing effects in cancer.
  • Therapeutic strategies must carefully modulate the pathway to harness anti-tumor effects and avoid immune suppression.
  • Balancing pathway activation is key to effective cancer immunotherapy.

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