{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:51:42Z","timestamp":1788274302226,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institut National de la Sante et de la Recherche M\u00e9dicale, Universit\u00e9 de Strasbourg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: PC is the second most common malignancy in men, and progression to metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT) remains incurable. Current treatments for mCRPC include chemotherapy, immunotherapy, radiopharmaceuticals, and second-line androgen receptor signaling inhibitors (ARSIs) such as Abiraterone. PARP inhibitors (PARPis) have recently shown clinical benefits in tumors with homologous recombination repair (HRR) deficiencies, particularly BRCA1\/2 mutations. Combining PARPi with ARSIs has improved progression-free (PFS) and overall survival (OS), especially in ARSI-na\u00efve patients, but limited data exist for resistant disease. Objectives: This work focuses on intrinsically hormone-insensitive, AR-negative, BRCA-wildtype models, representing a clinically distinct population with limited therapeutic options. We thus investigated the therapeutic potential of combining Abiraterone with PARPis (Niraparib or Olaparib) in Abiraterone-resistant prostate cancer. Methods: Resistant PC3 and DU145 cell lines were analyzed using 2D and 3D cultures and cell-derived xenograft (CDX) mouse models. Results: Cytotoxicity assays revealed significantly reduced cell viability with combination therapy compared to single agents. These findings were supported by RT-qPCR, Western blot, and immunofluorescence analyses of xenograft tumors, demonstrating enhanced antitumor activity with the combination. Conclusions and significance: Overall, the results indicate that maintaining Abiraterone treatment in combination with PARPis after resistance develops provides superior therapeutic efficacy compared to PARP inhibition alone, offering a promising strategy for managing Abiraterone-resistant prostate cancer. Combining Abiraterone with PARPis enhances therapeutic efficacy and overcomes the acquired insensitivity in mCRPC with BRCA1\/2 or HRR mutations. These results support continued use of PARPis with Abiraterone to improve clinical outcomes.<\/jats:p>","DOI":"10.3390\/cancers18040560","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T12:42:42Z","timestamp":1770640962000},"page":"560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PARP Inhibitors Combined with Abiraterone Overcome Resistance in Metastatic Castration-Resistant Prostate Cancer Independently of Androgen Receptor"],"prefix":"10.3390","volume":"18","author":[{"given":"Hamza","family":"Mallah","sequence":"first","affiliation":[{"name":"French National Institute of Health and Medical Research (INSERM), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"},{"name":"Universit\u00e9 de Strasbourg, UMR 1260, CRBS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Soultani","sequence":"additional","affiliation":[{"name":"French National Institute of Health and Medical Research (INSERM), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"},{"name":"Universit\u00e9 de Strasbourg, UMR 1260, CRBS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zania","family":"Diabasana","sequence":"additional","affiliation":[{"name":"French National Institute of Health and Medical Research (INSERM), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"},{"name":"Universit\u00e9 de Strasbourg, UMR 1260, CRBS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5140-5321","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Lindner","sequence":"additional","affiliation":[{"name":"Department of Pathology, Strasbourg University Hospital, 67200 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Barth\u00e9l\u00e9my","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Strasbourg, 1 Avenue Moli\u00e8re, 67200 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ysia","family":"Idoux-Gillet","sequence":"additional","affiliation":[{"name":"French National Institute of Health and Medical Research (INSERM), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"},{"name":"Universit\u00e9 de Strasbourg, UMR 1260, CRBS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5114-2744","authenticated-orcid":false,"given":"Thierry","family":"Massfelder","sequence":"additional","affiliation":[{"name":"French National Institute of Health and Medical Research (INSERM), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"},{"name":"Universit\u00e9 de Strasbourg, UMR 1260, CRBS, 1 Rue Eug\u00e8ne Boeckel, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.14740\/wjon1191","article-title":"Epidemiology of Prostate Cancer","volume":"10","author":"Rawla","year":"2019","journal-title":"World J. 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