{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T06:59:36Z","timestamp":1772866776595,"version":"3.50.1"},"reference-count":35,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>This study aimed to define molecular subtypes of prostate cancer by integrating androgen receptor (AR) signaling, neuroendocrine prostate cancer (NEPC) transcriptional signatures, and genomic alterations to inform biomarker-driven therapies in metastatic castration-resistant prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed 8,019 prostate tumors using DNA\/RNA sequencing (Caris Life Sciences), classifying them into four molecular subtypes (AR+\/NE\u2013, AR\u2013\/NE+, AR+\/NE+, AR\u2013\/NE\u2013). Genomic alterations, cell surface target expression, and overall survival (OS) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Of the 8,019 tumors, 87.2% were adenocarcinoma, 1.9% NEPC, and 0.4% had mixed histology; 63% were from primary sites and 36.5% from metastases. The median age was 68 years; 63% were White, 15% Black, and 2.6% Asian or Pacific Islander. Most tumors were classified as AR+\/NE\u2013 (91%), and 4.6% were AR-\/NE+. TP53 and PTEN alterations were enriched in AR\u2013negative subtypes, whereas SPOP mutations were more frequent in AR+ tumors. FOLH1 (prostate-specific membrane antigen) expression was the highest in AR+ tumors, whereas DLL3 expression was elevated in NE+ tumors. Median OS was significantly longer in tumors with high AR signaling (55.0\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      14.0 months,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .00001) and lower with the NEPC signature (54.3\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      16.1 months,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .00001). Combined stratification showed the most favorable outcome in AR+\/NE\u2013 tumors (55.3 months) and the poorest in AR\u2013\/NE+ tumors (12.0 months).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Prostate cancer exhibits distinct molecular subtypes defined by AR signaling activity, NEPC transcriptional profiles, and genomic alterations. These biologically and clinically relevant subgroups provide a framework for precision oncology approaches and inform patient selection for biomarker-driven trials such as the ongoing PREDICT study (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT06632977\">NCT06632977<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00756","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T20:59:07Z","timestamp":1772744347000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Utility of Transcriptomic Signatures to Identify Androgen Receptor and Neuroendocrine Signaling in Prostate Cancer"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7988-319X","authenticated-orcid":true,"given":"Yu-Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Hematology Oncology, Department of Medicine, University of California San Diego School of Medicine, San Diego, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Xiu","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey Anne","family":"Poorman","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles J.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Memorial Sloan Ketter Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5112-8992","authenticated-orcid":true,"given":"Brady","family":"Gilg","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-2513","authenticated-orcid":true,"given":"Matthew James","family":"Oberley","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4817-458X","authenticated-orcid":true,"given":"Gloria","family":"Sura","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-0775","authenticated-orcid":true,"suffix":"Jr","given":"George W.","family":"Sledge","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-6507","authenticated-orcid":true,"given":"Shuang G.","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of Wisconsin Department of Human Oncology, Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6350-5917","authenticated-orcid":true,"given":"Alan","family":"Tan","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3259-2226","authenticated-orcid":true,"given":"Himisha","family":"Beltran","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 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