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Cancer cell-autonomous cGAS-STING response confers drug resistance

Qian-Ming Lv1, Hui-Min Lei1, Shi-Yi Wang1

  • 1Department of Pharmacology and Chemical Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Cell Chemical Biology
|June 1, 2023
PubMed

Insights

Cancer cells activate the cGAS-STING pathway to resist chemotherapy. Blocking stimulator of interferon genes (STING) signaling overcomes this drug resistance, revealing a new therapeutic target.

Area of Science:

  • Immunology
  • Cancer Biology
  • Pharmacology

Background:

  • The cGAS-STING pathway is known for immune surveillance and tumor suppression.
  • Its role in cancer cell-intrinsic drug resistance is not well understood.

Purpose of the Study:

  • To investigate the role of the cGAS-STING pathway in cancer drug resistance.
  • To explore the potential of targeting STING signaling to overcome treatment resistance.

Main Methods:

  • Activation of the cGAS-STING pathway in cancer cells treated with chemotherapy drugs.
  • Analysis of downstream signaling (TBK1-IRF3/NF-κB).
  • In vitro and in vivo models to test STING blockade efficacy.

Main Results:

  • Chemotherapy induces cytosolic DNA accumulation, activating the cGAS-STING pathway in cancer cells.
  • This intrinsic pathway confers resistance to targeted and conventional chemotherapy.
  • STING signaling blockade delays and overcomes drug resistance in preclinical models.

Conclusions:

  • The cGAS-STING pathway mediates cancer cell-autonomous drug resistance.
  • Targeting STING offers a strategy to overcome chemotherapy resistance.
  • Caution is advised for combining STING agonists with chemotherapy due to potential resistance.
Keywords:
Cancer cell-autonomousDrug resistanceSTINGcGAS

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