A1 Refereed original research article in a scientific journal
Multi-omics analysis reveals the attenuation of the interferon pathway as a driver of chemo-refractory ovarian cancer
Authors: Afenteva, Daria; Yu, Rong; Rajavuori, Anna; Salvadores, Marina; Launonen, Inga-Maria; Lavikka, Kari; Zhang, Kaiyang; Pirttikoski, Anna; Marchi, Giovanni; Jamalzadeh, Sanaz; Isoviita, Veli-Matti; Li, Yilin; Micoli, Giulia; Erkan, Erdogan Pekcan; Falco, Matias M.; Ungureanu, Daniela; Lahtinen, Alexandra; Oikkonen, Jaana; Hietanen, Sakari; Vähärautio, Anna; Sur, Inderpreet; Virtanen, Anni; Färkkilä, Anniina; Hynninen, Johanna; Muranen, Taru A.; Taipale, Jussi; Hautaniemi, Sampsa
Publisher: Cell Press
Publication year: 2025
Journal: Cell Reports Medicine
Journal name in source: Cell Reports Medicine
Article number: 102316
Volume: 6
Issue: 9
eISSN: 2666-3791
DOI: https://doi.org/10.1016/j.xcrm.2025.102316
Web address : https://doi.org/10.1016/j.xcrm.2025.102316
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/499884655
Ovarian high-grade serous carcinoma (HGSC) is one of the deadliest gynecological malignancies, with 10%–15% of patients exhibiting primary resistance to first-line chemotherapy. To characterize the molecular drivers of chemo-refractoriness, we perform multi-omics profiling of treatment-naive biopsies from patients with refractory HGSC enrolled in the DECIDER observational trial. We demonstrate that chemo-refractory HGSC is characterized by diminished interferon type I (IFN-I) and enhanced hypoxia pathway activity, and baseline IFN-I activity in chemo-naive cancer is an independent prognostic factor. Single-cell RNA sequencing and spatial protein profiling analyses corroborate the importance of elevated IFN-I activity in response to chemotherapy. Importantly, in vitro experiments demonstrate that high levels of IFN-I signaling increase cell chemosensitivity to platinum in a cell-autonomous manner. Together, these findings indicate that the IFN-I pathway activity in HGSC cancer cells predicts response to first-line chemotherapy in HGSC, proposing the stimulation of the IFN-I response as a therapeutic strategy. The study is registered at ClinicalTrials.gov (NCT04846933).
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Funding information in the publication:
This project received funding from the European Union’s Horizon 2020 Research and Innovation Program under grant agreement 965193 (DECIDER), the Research Council of Finland, the Sigrid Jusélius Foundation, the Cancer Foundation Finland, Cancerfonden (Sweden), and the Swedish Research Council. This study was co-funded by the European Union (ERC, SPACE 101076096).
