{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:25:09Z","timestamp":1783571109540,"version":"3.55.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The development of therapy resistance and the formation of distant metastases represent clinical unmet needs for patients with advanced prostate cancer (PCa). The use of drugs for other indications, i.e. drug repurposing, shows great promise for cancer treatment. Drug repurposing could allow new cancer treatments to be introduced relatively quickly and at lower costs. Penfluridol, an approved antipsychotic drug, has strong cytolytic effects in multiple cancers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we have investigated the potential anti-tumor effects of penfluridol in preclinical and \u2018near-patient\u2019 PCa models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Penfluridol significantly reduced the viability of a panel of human PCa cells, induced apoptosis by increasing caspase-3\/7 levels and decreased the number of PCa stem cells in vitro. Penfluridol reduced the viability and induced cytotoxic effects in three-dimensional cultures and in ex vivo cultured PCa tissue slices (patient-derived xenograft, freshly isolated PCa biopsies). Moreover, penfluridol significantly reduced the viability of docetaxel-resistant PCa cells and exerted synergistic effects in combination with docetaxel in docetaxel-resistant PCa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, penfluridol exhibited cytotoxic effects in multiple preclinical PCa models. Further research is warranted to address the translational value of our findings.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1685758","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:15:22Z","timestamp":1760415322000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti-neoplastic effects of the antipsychotic drug penfluridol in preclinical prostate cancer models"],"prefix":"10.3389","volume":"15","author":[{"given":"Arjanneke F.","family":"van de Merbel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike H.","family":"van der Mark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilly","family":"Aalders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Puhr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niven","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Schalken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geertje","family":"van der Horst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabri","family":"van der Pluijm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040720","article-title":"Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer","volume":"351","author":"Tannock","year":"2004","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/jech.43.1.43","article-title":"The incidence of cancer in schizophrenic patients","volume":"43","author":"Mortensen","year":"1989","journal-title":"J Epidemiol Community Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbs065","article-title":"Incidence of cancer in patients with schizophrenia and their first-degree relatives: a population-based study in Sweden","volume":"39","author":"Ji","year":"2013","journal-title":"Schizophr Bull"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2006.08.1061","article-title":"Prostate cancer and schizophrenia","volume":"68","author":"Torrey","year":"2006","journal-title":"Urology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2017.08.065","article-title":"The incidence rate of cancer in patients with schizophrenia: A meta-analysis of cohort studies","volume":"195","author":"Li","year":"2018","journal-title":"Schizophr Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2008.01163.x","article-title":"Cancer incidence in patients with schizophrenia and their first-degree relatives - a meta-analysis","volume":"117","author":"Catts","year":"2008","journal-title":"Acta Psychiatr Scand"},{"key":"B8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.2165\/00003088-198713020-00001","article-title":"Antipsychotic drugs. 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