{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:34:03Z","timestamp":1786696443687,"version":"build-2736575974"},"reference-count":327,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Epithelial ovarian cancer (EOC) remains a gynecologic malignancy with a poor prognosis, with a 5-year survival of approximately 29% in advanced-stage disease. Despite cytoreductive surgery and platinum- and taxane-based chemotherapy, most patients relapse within 2 years. Major therapeutic barriers include chemoresistance, molecular heterogeneity, and an immunosuppressive peritoneal microenvironment. This review summarizes emerging therapeutic strategies for EOC, their mechanisms of action, and their potential to overcome treatment resistance. Methods: PubMed\/MEDLINE was searched for preclinical studies, phase I\u2013III clinical trials, systematic reviews, and meta-analyses addressing novel ovarian cancer therapies and resistance mechanisms. Results: The review covers molecularly targeted therapies, immunotherapies, metabolic and epigenetic approaches, cellular and gene therapies, targeted drug-delivery systems, and locoregional and physical modalities. Strategies include PARP inhibitors, antiangiogenic agents, antibody\u2013drug conjugates, pathway inhibitors, immune checkpoint inhibitors, cancer vaccines, adoptive cell therapies, metabolic and epigenetic modulators, CAR-T, CAR-NK, CRISPR\/Cas9, HIPEC, PIPAC, ablation, photodynamic therapy, and sonodynamic therapy. Conclusions: The clinical maturity of these approaches varies substantially. PARP inhibitors, antiangiogenic agents, selected antibody\u2013drug conjugates, MAPK-directed therapy in LGSOC, and HIPEC in selected settings have the strongest clinical support. Most immune combinations, metabolic and epigenetic therapies, adoptive cell therapies, gene-editing approaches, and novel delivery or physical modalities remain early clinical or predominantly preclinical. Progress will depend on biomarker-guided patient selection, reassessment of evolving resistance mechanisms, and rational treatment sequencing and combinations.<\/jats:p>","DOI":"10.3390\/cancers18162623","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:08:29Z","timestamp":1786694909000},"page":"2623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Overcoming Therapy Resistance in Ovarian Cancer: From Molecular Mechanisms to Emerging Therapeutic Strategies"],"prefix":"10.3390","volume":"18","author":[{"given":"Zofia","family":"Pietrasik","sequence":"first","affiliation":[{"name":"Department of Pathophysiology of Aging and Civilization Diseases, Poznan University of Medical Sciences, Swiecickiego 4 Str., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miko\u0142aj","family":"Kapa\u0142a","sequence":"additional","affiliation":[{"name":"Medical University of \u0141\u00f3d\u017a, Al. 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Ko\u015bciuszki 4 Str., 90-419 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Pietrasik","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Aging and Civilization Diseases, Poznan University of Medical Sciences, Swiecickiego 4 Str., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5404-2957","authenticated-orcid":false,"given":"Monika","family":"Stefaniak","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Faculty of Medical Sciences, Prince Mieszko I Pozna\u0144 Medical University of Applied Sciences, Bu\u0142garska 55 Str., 60-320 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-7188","authenticated-orcid":false,"given":"Sebastian","family":"Szubert","sequence":"additional","affiliation":[{"name":"Department of Gynecological Oncology, Institute of Oncology, University of Medical Sciences, 82\/84 Szamarzewskiego Str., 60-569 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6066-5747","authenticated-orcid":false,"given":"Krzysztof","family":"Ksi\u0105\u017cek","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Faculty of Medical Sciences, Prince Mieszko I Pozna\u0144 Medical University of Applied Sciences, Bu\u0142garska 55 Str., 60-320 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8267-5428","authenticated-orcid":false,"given":"Justyna","family":"Miku\u0142a-Pietrasik","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Aging and Civilization Diseases, Poznan University of Medical Sciences, Swiecickiego 4 Str., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1001\/jama.2025.9495","article-title":"Ovarian Cancer: A Review","volume":"334","author":"Caruso","year":"2025","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1002\/ijc.34002","article-title":"Ovarian cancer today and tomorrow: A global assessment by world region and Human Development Index using GLOBOCAN 2020","volume":"151","author":"Cabasag","year":"2022","journal-title":"Int. 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