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cGAS-STING signaling pathway in urogenital oncology: Regulation, resistance, and routes to response

Chen Gong1, Senmao Li2, Yinglong Huang2

  • 1Department of Urology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China; Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Street, Wuhua District, Kunming, Yunnan 650101, PR China; Urological Disease Clinical Medical Center of Yunnan Province, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Street, Wuhua District, Kunming, Yunnan 650101, PR China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Street, Wuhua District, Kunming, Yunnan 650101, PR China.

Critical Reviews in Oncology/Hematology
|February 19, 2026
PubMed

Insights

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is crucial in urogenital cancers, influencing tumor behavior and immune response. Targeting this pathway offers new therapeutic strategies for cancer treatment.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a key mediator of innate immunity, linking cytosolic DNA detection to cellular responses.
  • This pathway plays a complex and paradoxical role in urogenital cancers, significantly influencing tumor progression and the tumor microenvironment.

Purpose of the Study:

  • To review and synthesize recent advances in understanding the multilayered regulation of the cGAS-STING pathway in urogenital cancers.
  • To explore emerging therapeutic strategies that modulate the cGAS-STING axis for cancer immunotherapy.
  • To highlight the challenges and opportunities in translating these findings into clinical practice.

Main Methods:

  • Literature review of recent research on cGAS-STING pathway regulation and therapeutic applications in urogenital oncology.
  • Analysis of multilayered regulatory mechanisms including phosphorylation, ubiquitination, epigenetics, and metabolic reprogramming.
  • Evaluation of therapeutic strategies such as genomic instability exploitation, STING reactivation, and direct pathway engagement.

Main Results:

  • The cGAS-STING pathway is subject to intricate regulation, impacting tumor-immune communication and shaping cancer cell behavior.
  • Therapeutic strategies involving cGAS-STING activation, alone or in combination with other immunotherapies, show promise but also reveal resistance mechanisms.
  • Biomarker frameworks and patient-derived models are emerging to guide clinical translation and personalize treatment.

Conclusions:

  • The cGAS-STING pathway represents a critical, yet complex, target in urogenital oncology, offering significant potential for immune reactivation.
  • Precision strategies are necessary to overcome resistance and harness the full therapeutic potential of cGAS-STING modulation.
  • Further research into non-canonical signaling and intercellular transport is vital for optimizing therapeutic interventions.
Keywords:
BiomarkersBladder cancerCGAS–STING pathwayDNA damage responseImmunotherapyProstate cancer

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