{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:12:08Z","timestamp":1773803528659,"version":"3.50.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust Clinical Research Career Development Fellowship","award":["219594\/Z\/19\/Z"],"award-info":[{"award-number":["219594\/Z\/19\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clival metastases are a rare and clinically aggressive manifestation of advanced prostate cancer, associated with cranial nerve palsy and poor survival. The molecular features of prostate cancers giving rise to clivus metastases remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We performed a multi-center retrospective study across six institutions, identifying prostate cancer patients with radiographically confirmed clival metastases and available next-generation sequencing (NGS) data. Baseline characteristics and clinical outcomes were collected. Genomic alterations from tissue- and\/or blood-based assays were aggregated at the patient level and compared with a publicly available metastatic castration-resistant prostate cancer (mCRPC) cohort (SU2C\/PCF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty-nine patients with clival metastases contributed 87 molecular assays. More than half of patients had Gleason grade group 5 cancer and presented with de novo metastatic (M1) disease. The median interval from initial prostate cancer diagnosis to clival metastasis was 71.4\u2009months (95% CI, 42.0-101.7), while median overall survival following clival involvement was only 15.3\u2009months (95% CI, 6.9-22.8). Compared with the SU2C\/PCF mCRPC cohort, clival metastases showed significant enrichment of BRAF and CHEK2 alterations as well as homologous recombination repair (HRR) with relative depletion of AR-related, PI3K pathway, and G2\u2013M pathway alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Prostate cancers giving rise to clival metastases exhibit a distinct molecular profile enriched for DNA damage\u2013repair and RAF kinase alterations, suggesting unique metastatic biology and potential therapeutic vulnerabilities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag074","type":"journal-article","created":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T12:34:00Z","timestamp":1772368440000},"source":"Crossref","is-referenced-by-count":0,"title":["Molecular landscape of prostate cancers with clival metastases"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9689-3231","authenticated-orcid":false,"given":"Pornlada","family":"Likasitwatanakul","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Minnesota-Twin Cities , Minneapolis, MN 55455,","place":["United States"]},{"name":"Department of Medicine, Siriraj Hospital, Mahidol University , Bangkok, 10700,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0776-5677","authenticated-orcid":false,"given":"Steven M","family":"Blinka","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center , Seattle, WA 98109,","place":["United States"]},{"name":"Division of Hematology and Oncology, University of Washington School of Medicine , Seattle, WA 98195,","place":["United 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10021,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0203-3987","authenticated-orcid":false,"given":"Ossian","family":"Longoria","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research Division of Clinical Studies, , London, SM2 5GP,","place":["United Kingdom"]},{"name":"The Royal Marsden NHS Foundation Trust Drug Development Unit and Prostate Cancer Targeted Therapy Group, , London, SM2 5PT,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-1666","authenticated-orcid":false,"given":"Joseph A","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Minnesota-Twin Cities , Minneapolis, MN 55455,","place":["United 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Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cora N","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Weill Cornell Medicine and the Englander Institute for Precision Medicine , New York, NY 10021,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1076-0428","authenticated-orcid":false,"given":"Neeraj","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Oncology, University of Utah Huntsman Cancer Institute , Salt Lake City, UH 84112,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3518-0411","authenticated-orcid":false,"given":"Umang","family":"Swami","sequence":"additional","affiliation":[{"name":"Division of Oncology, University of Utah Huntsman Cancer Institute , Salt Lake City, UH 84112,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-0239","authenticated-orcid":false,"given":"Jacob J","family":"Orme","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5510-0661","authenticated-orcid":false,"given":"Michael T","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center , Seattle, WA 98109,","place":["United States"]},{"name":"Division of Hematology and Oncology, University of Washington School of Medicine , Seattle, WA 98195,","place":["United 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