{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T06:15:14Z","timestamp":1763619314457,"version":"3.45.0"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","award":["RTI2018-094533-A-I00"],"award-info":[{"award-number":["RTI2018-094533-A-I00"]}]},{"name":"\u00abPROYECTOS DE GENERACI\u00d3N DE CONOCIMIENTO\u00bb","award":["PID2021-128644OB-I0"],"award-info":[{"award-number":["PID2021-128644OB-I0"]}]},{"name":"ERDF\/EU"},{"DOI":"10.13039\/100008050","name":"CELLEX foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005677","name":"Jos\u00e9 Carreras Leuk\u00e4mie-Stiftung","doi-asserted-by":"crossref","award":["DJCLS 19R\/2022"],"award-info":[{"award-number":["DJCLS 19R\/2022"]}],"id":[{"id":"10.13039\/501100005677","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca-Generalitat de Catalunya","award":["2021-SGR-00284"],"award-info":[{"award-number":["2021-SGR-00284"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Metastatic castration-resistant prostate cancer (mCRPC) remains a major clinical challenge due to its aggressive behavior and resistance to therapy. Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in various cancers and associated with poor prognosis. YM155 (Sepantronium bromide) suppresses survivin expression and has demonstrated antitumor activity in preclinical models. We investigated the association between survivin expression and clinical outcomes in mCRPC patients and evaluated the antitumor activity of YM155, alone and in combination with carboplatin, in mCRPC cell lines. Methods: Analysis of publicly available RNA-seq datasets from mCRPC patients was performed to assess correlations between survivin expression and clinical outcomes. Radiographic progression-free survival (rPFS) and overall survival (OS) were estimated using the Kaplan\u2013Meier method and compared via log-rank or Fisher\u2019s exact tests. In vitro assays were conducted on mCRPC cell lines treated with YM155, carboplatin, or both, to evaluate cell viability, clonogenicity, and apoptosis. Results: Survivin was significantly overexpressed in mCRPC compared with localized prostate cancer and was even higher in castration-resistant neuroendocrine disease. High survivin levels were associated with shorter OS (p = 0.006). In patients treated with platinum-based therapies, high survivin was also linked to shorter rPFS (p = 0.01), reduced OS (p = 0.006), and a smaller PSA decline (p = 0.006). In vitro, YM155 reduced survivin expression, impaired cell viability and colony formation, induced apoptosis, and synergistically enhanced the cytotoxicity of carboplatin. Conclusions: Our findings suggest that survivin may serve as a prognostic biomarker and potential therapeutic target in platinum-treated, AR-independent mCRPC. The integration of clinical and functional data provides translational support for combining the survivin inhibitor YM155 with platinum-based therapy. These results warrant further validation in larger patient cohorts and in vivo models.<\/jats:p>","DOI":"10.3390\/ph18111752","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:05:31Z","timestamp":1763463931000},"page":"1752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["YM155 Inhibition of Survivin Enhances Carboplatin Efficacy in Metastatic Castration-Resistant Prostate Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4352-1784","authenticated-orcid":false,"given":"Vicen\u00e7","family":"Ruiz de Porras","sequence":"first","affiliation":[{"name":"GRET and Toxicology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8803-2485","authenticated-orcid":false,"given":"Martin K.","family":"Bakht","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Fernandez-Saor\u00edn","sequence":"additional","affiliation":[{"name":"CARE Program, Germans Trias i Pujol Research Institute (IGTP), Cam\u00ed de les Escoles, s\/n, 08916 Badalona, Spain"},{"name":"Badalona Applied Research Group in Oncology (B-ARGO), Catalan Institute of Oncology, Cam\u00ed de les Escoles, s\/n, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Alcon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9144-1017","authenticated-orcid":false,"given":"Luis","family":"Palomero","sequence":"additional","affiliation":[{"name":"Department Llenguatges i Sistemes Inform\u00e0tics, Institute of New Imaging Technologies, Universitat Jaume I, Av. Sos Baynat s\/n, 12071 Castell\u00f3n de la Plana, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00falia","family":"Francisco-Rodon","sequence":"additional","affiliation":[{"name":"CARE Program, Germans Trias i Pujol Research Institute (IGTP), Cam\u00ed de les Escoles, s\/n, 08916 Badalona, Spain"},{"name":"Badalona Applied Research Group in Oncology (B-ARGO), Catalan Institute of Oncology, Cam\u00ed de les Escoles, s\/n, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-3812","authenticated-orcid":false,"given":"Mariona","family":"Figols","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Althaia Xarxa Assistencial Universit\u00e0ria de Manresa, C\/Dr. Joan Soler, 1-3, 08243 Manresa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Montero","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08007 Barcelona, Spain"},{"name":"Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-714X","authenticated-orcid":false,"given":"Vincenza","family":"Conteduca","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Himisha","family":"Beltran","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Font","sequence":"additional","affiliation":[{"name":"CARE Program, Germans Trias i Pujol Research Institute (IGTP), Cam\u00ed de les Escoles, s\/n, 08916 Badalona, Spain"},{"name":"Badalona Applied Research Group in Oncology (B-ARGO), Catalan Institute of Oncology, Cam\u00ed de les Escoles, s\/n, 08916 Badalona, Spain"},{"name":"Department of Medical Oncology, Catalan Institute of Oncology (ICO), 08907 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0140-6736(21)00950-8","article-title":"Prostate cancer","volume":"398","author":"Sandhu","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.euf.2016.11.012","article-title":"The Molecular Evolution of Castration-resistant Prostate Cancer","volume":"2","author":"Ceder","year":"2016","journal-title":"Eur. 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