cGAS-STING pathway in oncogenesis and cancer therapeutics

Brandon Yi Da Hoong1,2,3, Yunn Hwen Gan1,2,4, Haiyan Liu2,5

  • 1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Oncotarget
|August 11, 2020
PubMed

Insights

The cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon (IFN) genes (STING) pathway detects DNA damage, aiding cancer immunosurveillance. Understanding this pathway offers new therapeutic targets but requires caution due to potential links to carcinogenesis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Innate immunity acts as the first defense against pathogens.
  • The cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon (IFN) genes (STING) pathway senses cytoplasmic DNA from genomic instability.
  • This pathway is crucial for detecting DNA damage and cell cycle defects.

Purpose of the Study:

  • To review recent findings on cGAS-STING pathway regulation in cancer immunosurveillance.
  • To explore downstream signaling in immune cell recruitment and tumor destruction.
  • To discuss the cGAS-STING pathway as a therapeutic target and potential risks.

Main Methods:

  • Literature review of recent insights into cGAS-STING pathway regulation.
  • Analysis of downstream signaling cascades in the tumor microenvironment.
  • Discussion of cancer cell evasion mechanisms and chronic activation effects.

Main Results:

  • The cGAS-STING pathway mediates cancer immunosurveillance by promoting cellular senescence or death.
  • It recruits immune cells to the tumor microenvironment.
  • Cancer cells develop adaptive mechanisms to evade cGAS-STING signaling.

Conclusions:

  • The cGAS-STING pathway is a promising target for anti-cancer immunotherapies, such as agonists or vaccine adjuvants.
  • Targeting cGAS-STING in synthetic lethality approaches is suggested.
  • Chronic cGAS-STING activation may promote inflammation-induced carcinogenesis, necessitating careful therapeutic application.

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