{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:27:27Z","timestamp":1793647647216,"version":"4.5.1"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031283","name":"Sanofi France","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100031283","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Predictive biomarkers to guide chemotherapy decisions for metastatic castration\u2013resistant prostate cancer (mCRPC) are lacking. Preclinical studies indicate that circulating tumor cell (CTC) studies of chromosomal instability (CTC-CIN) can predict taxane resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      The CARD trial randomized individuals with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate plus prednisolone\/prednisone) to cabazitaxel or the alternative ARPI. As a preplanned biomarker analysis, CTCs were isolated from blood samples obtained at baseline, cycle 2, and the end of treatment. Associations between baseline CTC and CTC-CIN counts with imaging-based progression-free survival (ibPFS), overall survival (OS), time to prostate-specific antigen (PSA) progression, RECIST 1.1 objective response rate (ORR), and PSA\n                      <jats:sub>50<\/jats:sub>\n                      response rate were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      High baseline CTC-CIN counts significantly associated with worse OS after adjustment for confounding variables (median OS, 15.3 vs. 8.9 months; univariate HR, 2.16; 95% CI, 1.52\u20133.06;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001; multivariate HR, 1.56; 95% CI, 1.01\u20132.43;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.047). Detectable CTC-CIN counts at baseline may predict a lack of ibPFS and OS benefit when comparing cabazitaxel with ARPI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>This preplanned analysis of biomarker data from the CARD trial confirms that CTC-CIN counts are a clinically useful prognostic and predictive biomarker of taxane resistance in mCRPC. Detectable CTC-CIN at baseline defines a patient subpopulation with unmet clinical needs in which alternative therapeutics should be tested.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov number NCT02485691.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Funded by Sanofi and Epic Sciences.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.196505","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T17:01:41Z","timestamp":1762275701000},"source":"Crossref","is-referenced-by-count":1,"title":["Chromosomal instability in circulating tumor cells and cabazitaxel resistance in metastatic castration-resistant prostate cancer"],"prefix":"10.1172","volume":"10","author":[{"given":"Ossian","family":"Longoria","sequence":"first","affiliation":[{"name":"The Institute of Cancer Research, London, United Kingdom."},{"name":"The Royal Marsden NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rekowski","sequence":"additional","affiliation":[{"name":"Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Epic Sciences, San Diego, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Beije","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research, London, United Kingdom."},{"name":"The Royal Marsden NHS Foundation Trust, London, United Kingdom."},{"name":"Erasmus MC Cancer Institute, 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