Ovarian high-grade serous carcinoma (HGSC) represents the deadliest gynecological malignancy, with 10-15% of patients exhibiting primary resistance to first-line chemotherapy. These primarily chemo-refractory patients have particularly poor survival outcomes, emphasizing the urgent need for developing predictive biomarkers and novel therapeutic approaches. Here, we show that interferon type I (IFN-I) pathway activity in cancer cells is a crucial determinant of chemotherapy response in HGSC. Through a comprehensive multi-omics analysis within the DECIDER observational trial (ClinicalTrials.gov identifier NCT04846933) cohort, we identified that chemo-refractory HGSC is characterized by diminished IFN-I and enhanced hypoxia pathway activities. Importantly, IFN-I pathway activity was independently prognostic for patient survival, highlighting its potential as a biomarker. Our results elucidate the heterogeneity of treatment response at the molecular level and suggest that augmentation of IFN-I response could enhance chemosensitivity in refractory cases. This study underscores the potential of the IFN-I pathway as a therapeutic target and advocates for the initiation of clinical trials testing external modulators of the IFN-I response, promising a significant stride forward in the treatment of refractory HGSC.
Multi-omics analysis reveals the attenuation of the interferon pathway as a driver of chemo-refractory ovarian cancer
D. Afenteva,R. Yu,A. Rajavuori,Marina Salvadores,I.-M. Launonen,K. Lavikka,Kaiyang Zhang,G. Marchi,S. Jamalzadeh,V. Isoviita,Yilin Li,Giulia Micoli,E. Erkan,Matias M. Falco,Daniela Ungureanu,A. Lahtinen,J. Oikkonen,S. Hietanen,Anna Vähärautio,I. Sur,A. Virtanen,A. Färkkilä,J. Hynninen,T. Muranen,J. Taipale,S. Hautaniemi
Published 2024 in bioRxiv
ABSTRACT
PUBLICATION RECORD
- Publication year
2024
- Venue
bioRxiv
- Publication date
2024-03-30
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
- No claims are published for this paper.
CONCEPTS
- No concepts are published for this paper.
REFERENCES
Showing 1-99 of 99 references · Page 1 of 1
CITED BY
Showing 1-7 of 7 citing papers · Page 1 of 1