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FGFR1 Suppresses STING-Mediated Interferon Response in Endocrine Therapy-Resistant Breast Cancer

Torbjørn Amundsen Lien1, Sushil Dhakal1, Anne Marthe Fosdahl Wium1

  • 1Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Cancer Research Communications
|August 19, 2026
PubMed

Insights

Fibroblast growth factor receptor 1 (FGFR1) suppresses the interferon response in tamoxifen-resistant breast cancer. Inhibiting FGFR1 re-sensitizes cells to tamoxifen and enhances the interferon pathway, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Fibroblast growth factor receptor 1 (FGFR1) amplification is common in ER⁺/HER2⁻ breast cancer, correlating with poor response to endocrine therapy.
  • The role of FGFR1 in regulating interferon (IFN) response during endocrine resistance is not well understood.

Purpose of the Study:

  • To investigate if FGFR1 modulates the IFN response via the cGAS-STING pathway in tamoxifen-resistant breast cancer.
  • To explore the therapeutic potential of targeting FGFR1 in overcoming endocrine resistance.

Main Methods:

  • Utilized tamoxifen-resistant ER⁺ breast cancer cell lines and a patient-derived xenograft (PDX) model.
  • Employed RNA sequencing, FGFR1 knockdown/inhibition, and functional assays.
  • Analyzed clinical relevance in breast cancer cohorts.

Main Results:

  • Tamoxifen-resistant cells showed increased cytosolic dsDNA and activated cGAS-STING pathway components (p-IRF3).
  • FGFR1 inhibition re-sensitized cells to tamoxifen, induced IFN response genes, and potentiated tamoxifen effects in vitro and in vivo.
  • FGFR1 knockdown enhanced STING-mediated IFNB1 expression in response to cytosolic DNA.
  • FGFR1 amplification correlated with poor prognosis in tumors with high STING1 expression (METABRIC cohort).

Conclusions:

  • FGFR1 acts as a suppressor of the cGAS-STING-mediated interferon response in tamoxifen-resistant ER⁺ breast cancer.
  • FGFR1's role in attenuating this response may contribute to tamoxifen resistance.
  • Targeting FGFR1 could be a novel strategy to enhance endocrine therapy efficacy.

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