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However, the cell\u2010autonomous role of IFN\u20101 in driving resistance in high\u2010grade serous ovarian cancer (HGSOC) remains unclear. Specifically, whether IFN\u20101 functions in HGSOC as solely a response to genotoxic stress due to genotoxic therapy as frontline treatment, or can independently act in driving resistance phenotypes, has not been studied. Utilizing a patient\u2010derived model of cisplatin\u2010sensitive (SE) and \u2010resistant (CR) HGSOC, we demonstrate that chronic cisplatin exposure is associated with enrichment of IFN\u20101 signaling and an interferon\u2010related DNA damage resistance signature. Acute cisplatin treatment elicited dynamic IFN\u20101 signaling in both SE and CR cells, indicating a conserved stress response. However, chronic, low\u2010level exposure to exogenous IFN\u03b2, without a DNA\u2010damaging agent, phenocopied several features of chronic cisplatin\u2010driven resistance, including reduced therapeutic sensitivity and decreased proliferation. Together, these findings identify IFN\u03b2 as a driver of resistance\u2010associated phenotypes and highlight cell\u2010autonomous IFN\u20101 signaling as a potential biomarker for resistance and therapeutic target in platinum\u2010resistant disease.<\/jats:p>","DOI":"10.1002\/1878-0261.70305","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:28:38Z","timestamp":1783686518000},"page":"2323-2339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interferon beta drives therapy resistance in a patient\u2010derived model of high\u2010grade serous ovarian cancer"],"prefix":"10.1002","volume":"20","author":[{"given":"Ashlyn","family":"Conant","sequence":"first","affiliation":[{"name":"Division of Biochemistry, Department of Basic Sciences Loma Linda University  California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tise","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Basic Sciences Loma Linda University  California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiera","family":"McGivney","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Basic Sciences Loma Linda University  California USA"},{"name":"Department of Biochemistry Whitworth University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2085-2588","authenticated-orcid":false,"given":"V. 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