{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:02:22Z","timestamp":1791914542216,"version":"4.3.4"},"reference-count":18,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"4","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precision Oncology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>In prostate cancer, inactivating CDK12 mutations lead to gene fusion\u2013induced neoantigens and possibly sensitivity to immunotherapy. We aimed to clinically, pathologically, and molecularly characterize CDK12-aberrant prostate cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We conducted a retrospective multicenter study to identify patients with advanced prostate cancer who harbored somatic loss-of-function CDK12 mutations. We used descriptive statistics to characterize their clinical features and therapeutic outcomes (prostate-specific antigen [PSA] responses, progression-free survival [PFS]) to various systemic therapies, including sensitivity to poly (ADP-ribose) polymerase and PD-1 inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Sixty men with at least monoallelic (51.7% biallelic) CDK12 alterations were identified across nine centers. Median age at diagnosis was 60.5 years; 71.7% and 28.3% were white and nonwhite, respectively; 93.3% had Gleason grade group 4-5; 15.4% had ductal\/intraductal histology; 53.3% had metastases at diagnosis; and median PSA was 24.0 ng\/mL. Of those who underwent primary androgen deprivation therapy for metastatic hormone-sensitive disease (n = 59), 79.7% had a PSA response, and median PFS was 12.3 months. Of those who received first-line abiraterone and enzalutamide for metastatic castration-resistant prostate cancer (mCRPC; n = 34), 41.2% had a PSA response, and median PFS was 5.3 months. Of those who received a first taxane chemotherapy for mCRPC (n = 22), 31.8% had a PSA response, and median PFS was 3.8 months. Eleven men received a PARP inhibitor (olaparib [n = 10], rucaparib [n = 1]), and none had a PSA response (median PFS, 3.6 months). Nine men received a PD-1 inhibitor as fourth- to sixth-line systemic therapy (pembrolizumab [n = 5], nivolumab [n = 4]); 33.3% had a PSA response, and median PFS was 5.4 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>CDK12-altered prostate cancer is an aggressive subtype with poor outcomes to hormonal and taxane therapies as well as to PARP inhibitors. A proportion of these patients may respond favorably to PD-1 inhibitors, which implicates CDK12 deficiency in immunotherapy sensitivity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po.19.00399","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T15:59:20Z","timestamp":1587484760000},"page":"370-381","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":195,"title":["<i>CDK12<\/i>\n                    -Altered Prostate Cancer: Clinical Features and Therapeutic Outcomes to Standard Systemic Therapies, Poly (ADP-Ribose) Polymerase Inhibitors, and PD-1 Inhibitors"],"prefix":"10.1200","author":[{"given":"Emmanuel S.","family":"Antonarakis","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Isaacsson Velho","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Fu","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Sacristan","family":"Santos","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Maughan","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Pili","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Adra","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora N.","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis J.","family":"Vlachostergios","sequence":"additional","affiliation":[{"name":"Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Tagawa","sequence":"additional","affiliation":[{"name":"Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan H.","family":"Bryce","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Scottsdale, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"McNatty","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Scottsdale, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachery R.","family":"Reichert","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Dreicer","sequence":"additional","affiliation":[{"name":"University of Virginia, Charlottesville, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Sartor","sequence":"additional","affiliation":[{"name":"Tulane University School of Medicine, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara L.","family":"Lotan","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Hussain","sequence":"additional","affiliation":[{"name":"Robert H. 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