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Personalized treatments, while effective in other cancers, remain underutilized in OC due to a lack of reliable biomarkers predicting clinical outcomes. Accordingly, precision medicine approaches are limited, with PARP inhibitors showing efficacy only in specific genetic contexts. Drug repurposing offers a promising, rapidly translatable strategy by leveraging existing pharmacological data to identify new treatments for OC. Patient\u2010derived polyclonal spheroids, isolated from ascites fluid closely mimic the clinical behavior of OC, providing a valuable model for drug testing. Using these spheroids, a high\u2010throughput drug screening pipeline capable of evaluating both cytotoxicity and anti\u2010migratory properties of a diverse drug library, including FDA\u2010approved, investigational, and newly approved compounds is developed. The findings highlight the importance of 3D culture systems, revealing a poor correlation between drug efficacy in traditional 2D models and more clinically relevant 3D spheroids. This approach has expedited the identification of promising candidates, such as rapamycin, which demonstrated limited activity as a monotherapy but synergized effectively with standard treatments like cisplatin and paclitaxel in vitro. In combination with platinum\u2010based therapy, Rapamycin led to significant in vitro cytotoxicity and a marked reduction in tumor burden in a syngeneic in vivo model. This proof\u2010of\u2010concept study underscores the potential of drug repurposing to rapidly advance new treatments into clinical trials for OC, offering renewed hope for patients with advanced disease.<\/jats:p>","DOI":"10.1002\/adhm.202404117","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:07:38Z","timestamp":1742447258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel 3D High\u2010Throughput Phenotypic Drug Screening Pipeline to Identify Drugs with Repurposing Potential for the Treatment of Ovarian Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Nazanin","family":"Karimnia","sequence":"first","affiliation":[{"name":"Hudson Institute of Medical Research  27\u201331 Wright St Clayton VIC 3168 Australia"},{"name":"Department of Molecular and Translational Sciences Monash University  45 Kanooka Grove Clayton VIC 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research  27\u201331 Wright St Clayton VIC 3168 Australia"},{"name":"Department of Molecular and Translational Sciences Monash University  45 Kanooka Grove Clayton VIC 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany R.","family":"Doran","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research  27\u201331 Wright St Clayton VIC 3168 Australia"},{"name":"Department of Molecular and Translational Sciences Monash University  45 Kanooka Grove Clayton VIC 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie","family":"Do","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research  27\u201331 Wright St Clayton VIC 3168 Australia"},{"name":"Department of Molecular and Translational Sciences Monash University  45 Kanooka Grove Clayton VIC 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Matthews","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research  27\u201331 Wright St Clayton VIC 3168 Australia"},{"name":"Department of Molecular and Translational Sciences Monash University  45 Kanooka Grove Clayton VIC 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwo Y.","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences Monash University  27 Rainforest Walk Clayton VIC 3168 Australia"},{"name":"Department of Oncology Monash Health  823\u2013865 Centre Rd Bentleigh VIC 3165 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Plebanski","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University Bundoora campus West  203, 1\/2 Plenty Rd Bundoora VIC 3083 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Jobling","sequence":"additional","affiliation":[{"name":"Monash Medical Centre Department of Gynecology Oncology Monash Health  823\u2013865 Centre Rd Bentleigh East VIC 3165 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research  27\u201331 Wright St Clayton VIC 3168 Australia"},{"name":"Department of Molecular and Translational Sciences Monash University  45 Kanooka Grove Clayton VIC 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9457-4333","authenticated-orcid":false,"given":"Maree","family":"Bilandzic","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research  27\u201331 Wright St Clayton VIC 3168 Australia"},{"name":"Department of Molecular and Translational Sciences Monash University  45 Kanooka Grove Clayton VIC 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"A. 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