{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:50:35Z","timestamp":1790898635334,"version":"4.1.0"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NCI","award":["R01CA178999,R01CA254403,R01CA301614,U54CA274513,5 T32 CA260293-02"],"award-info":[{"award-number":["R01CA178999,R01CA254403,R01CA301614,U54CA274513,5 T32 CA260293-02"]}]},{"name":"DOD","award":["PC220607,BC220744,LC240534"],"award-info":[{"award-number":["PC220607,BC220744,LC240534"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>VIC-1911 (formerly TAS-119) is a next-generation, ATP-competitive aurora kinase A (AURKA) inhibitor with a favorable biosafety profile. However, it has not been evaluated in prostate cancer (PCa), wherein AURKA is highly expressed in advanced stages and represents a critical therapeutic target. Here, we demonstrate that VIC-1911 potently inhibits AURKA activity with high selectivity over AURKB\/C across diverse PCa cell lines. Treatment with VIC-1911, even at nanomolar concentrations, substantially inhibits the growth of both androgen receptor\u2013positive (AR-positive) and AR-negative PCa cells. VIC-1911 triggers mitotic failure, induces DNA double-strand breaks (DSBs), and activates the p53 pathway, halting cell division and inducing cell death. Notably, VIC-1911 showed synergistic effects in inhibiting PCa cell growth in vitro and xenograft tumor growth in vivo with poly (ADP-ribose) polymerase inhibitors, which have proven effective in PCa with a deficiency in homologous recombination (HR) repair. Mechanistically, VIC-1911 disabled HR-mediated repair of DSBs in otherwise HR-proficient PCa cells, leading to a \u201cBRCAness\u201d phenotype and pronounced accumulation of DNA damage and mitotic catastrophe. In summary, our study uncovers what we believe is a novel mechanism to induce functional BRCAness through mitotic arrest and highlights VIC-1911 as a promising therapeutic agent for advanced PCa, either as a single agent or in combination, sensitizing HR-proficient tumors to PARP inhibitors.<\/jats:p>\n                  <jats:p\/>\n                  <jats:p>New-generation AURKA inhibitor VIC-1911 suppresses prostate cancer growth as a single agent and further increases sensitivity to PARP inhibitors.<\/jats:p>","DOI":"10.1172\/jci.insight.196665","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:00:23Z","timestamp":1774972823000},"source":"Crossref","is-referenced-by-count":3,"title":["AURKA inhibitor VIC-1911 induces mitotic defects and functional BRCAness, sensitizing prostate cancer to PARP inhibition"],"prefix":"10.1172","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3404-7961","authenticated-orcid":true,"given":"Galina","family":"Gritsina","sequence":"first","affiliation":[{"name":"Department of Urology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandip Kumar","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Urology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3293-7776","authenticated-orcid":true,"given":"Wanqing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Que Thanh Thanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Urology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sambhavi","family":"Senthil","sequence":"additional","affiliation":[{"name":"Department of Urology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Myers","sequence":"additional","affiliation":[{"name":"VITRAC Therapeutics LLC, Natick, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet A.","family":"Bilen","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Winship Cancer Institute of Emory University, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Fenton","sequence":"additional","affiliation":[{"name":"Robert H. 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