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Multi-omics analysis reveals the attenuation of the interferon pathway as a driver of chemo-refractory ovarian cancer

Daria Afenteva1, Rong Yu2, Anna Rajavuori3

  • 1Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Cell Reports. Medicine
|August 30, 2025
PubMed

Insights

Chemo-refractory ovarian cancer shows low interferon type I (IFN-I) signaling. Boosting IFN-I may improve chemotherapy response in high-grade serous carcinoma (HGSC) patients.

Area of Science:

  • Gynecologic Oncology
  • Cancer Genomics
  • Immunology

Background:

  • Ovarian high-grade serous carcinoma (HGSC) presents a significant challenge due to primary resistance to chemotherapy in 10-15% of cases.
  • Understanding the molecular basis of this chemo-refractoriness is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To identify molecular drivers of chemotherapy resistance in treatment-naive HGSC.
  • To investigate the role of interferon type I (IFN-I) signaling in predicting chemotherapy response.

Main Methods:

  • Multi-omics profiling of treatment-naive HGSC biopsies from the DECIDER trial.
  • Single-cell RNA sequencing and spatial protein profiling.
  • In vitro chemosensitivity assays.

Main Results:

  • Chemo-refractory HGSC exhibits diminished IFN-I pathway activity and enhanced hypoxia signaling.
  • Baseline IFN-I activity in chemo-naive tumors is an independent prognostic factor for treatment response.
  • High IFN-I signaling in cancer cells enhances sensitivity to platinum chemotherapy in vitro.

Conclusions:

  • IFN-I pathway activity is a predictive biomarker for first-line chemotherapy response in HGSC.
  • Stimulating the IFN-I response represents a potential therapeutic strategy to overcome chemo-resistance in HGSC.
Keywords:
chemo-refractory cancerchemoresistancecyclic immunofluorescenceinterferon type I signalingovarian cancerplatinum-based chemotherapyprospective clinical cohortreal-world datasingle-cell RNA sequencing

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