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The hypothesis guiding this study was that the inhibition of cell adhesion could be used as a novel strategy to increase the chemosensitivity of ovarian cancer cells. Methods: The Nectin-4 peptide N4-P10 was used to inhibit the formation of cell\u2013cell aggregates (spheroids) using cell lines and cells isolated from ovarian cancer patients\u2019 ascites. Cell lines were pre-treated with peptide N4-P10 or control scrambled peptides and monitored for spheroid formation with live-cell imaging by digital time-lapse photography. Cells were then tested for the cytotoxicity of the chemotherapeutic agent, cisplatin. Results: Peptide N4-P10 blocked aggregation in cell lines with different levels of Nectin-4 expression and different spheroid morphologies. The cytotoxicity of cisplatin increased in cells pre-treated with peptide N4-P10. Similarly, when single cells were isolated from the ascites of ovarian cancer patients, peptide N4-P10 blocked cell aggregation and increased the cytotoxicity of cisplatin. Conclusions: These results suggest that targeting the cell\u2013cell adhesive property of cancer cells could serve as a new approach to augment the cytotoxic effect of chemotherapy and potentially reduce disease recurrence in ovarian cancer patients.<\/jats:p>","DOI":"10.3390\/cancers17050901","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T06:02:13Z","timestamp":1741240933000},"page":"901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Peptide Derived from Nectin-4 Increases Cisplatin Cytotoxicity in Cell Lines and Cells from Ovarian Cancer Patients\u2019 Ascites"],"prefix":"10.3390","volume":"17","author":[{"given":"Kristin L. M.","family":"Boylan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Ovarian Cancer Early Detection Program, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin","family":"Walz","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra M.","family":"Schefter","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Women\u2019s Health, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4672-3450","authenticated-orcid":false,"given":"Amy P. N.","family":"Skubitz","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Ovarian Cancer Early Detection Program, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Obstetrics, Gynecology, and Women\u2019s Health, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3322\/caac.21456","article-title":"Ovarian cancer statistics, 2018","volume":"68","author":"Torre","year":"2018","journal-title":"CA Cancer J. 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