{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T16:18:32Z","timestamp":1771258712662,"version":"3.50.1"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":117,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MEDONC\/\n32222\/2017"],"award-info":[{"award-number":["PTDC\/MEDONC\/\n32222\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PD\/BD\/128288\/2017"],"award-info":[{"award-number":["PD\/BD\/128288\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K\/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K\/mTOR inhibition as a promising anticancer therapy to prevent late-stage metastatic brain cancer.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/noajnl\/vdad048","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T16:28:00Z","timestamp":1682699280000},"source":"Crossref","is-referenced-by-count":3,"title":["UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5915-8556","authenticated-orcid":false,"given":"Eunice","family":"Paisana","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa; Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Rita","family":"Casc\u00e3o","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa; Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Carlos","family":"Cust\u00f3dia","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa; Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3442-8043","authenticated-orcid":false,"given":"Nan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University D\u00fcsseldorf, Medical Faculty, and University Hospital D\u00fcsseldorf; Moorenstra\u00dfe 5 , 40225 D\u00fcsseldorf , Germany"},{"name":"German Cancer Consortium (DKTK) , Partner Site Essen\/D\u00fcsseldorf, D\u00fcsseldorf , Germany"},{"name":"Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf, Germany"}]},{"given":"Daniel","family":"Picard","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University D\u00fcsseldorf, Medical Faculty, and University Hospital D\u00fcsseldorf; Moorenstra\u00dfe 5 , 40225 D\u00fcsseldorf , Germany"},{"name":"German Cancer Consortium (DKTK) , Partner Site Essen\/D\u00fcsseldorf, D\u00fcsseldorf , Germany"},{"name":"Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf, Germany"}]},{"given":"David","family":"Pauck","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University D\u00fcsseldorf, Medical Faculty, and University Hospital D\u00fcsseldorf; Moorenstra\u00dfe 5 , 40225 D\u00fcsseldorf , Germany"},{"name":"German Cancer Consortium (DKTK) , Partner Site Essen\/D\u00fcsseldorf, D\u00fcsseldorf , Germany"},{"name":"Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf, Germany"}]},{"given":"T\u00e2nia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa; Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Pedro","family":"Ruivo","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa; Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Clara","family":"Barreto","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa; Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Delfim","family":"Doutel","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Department, Instituto Portugu\u00eas de Oncologia Francisco Gentil , R. Prof. Lima Basto, 1099-023, Lisboa , Portugal"}]},{"given":"Jos\u00e9","family":"Cabe\u00e7adas","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Department, Instituto Portugu\u00eas de Oncologia Francisco Gentil , R. Prof. Lima Basto, 1099-023, Lisboa , Portugal"}]},{"given":"Rafael","family":"Roque","sequence":"additional","affiliation":[{"name":"Neurology Department, Laboratory of Neuropathology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte (CHULN), Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Jos\u00e9","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Neurology Department, Laboratory of Neuropathology, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte (CHULN), Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Jos\u00e9","family":"Migu\u00e9ns","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte (CHULN), Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Marc","family":"Remke","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University D\u00fcsseldorf, Medical Faculty, and University Hospital D\u00fcsseldorf; Moorenstra\u00dfe 5 , 40225 D\u00fcsseldorf , Germany"},{"name":"German Cancer Consortium (DKTK) , Partner Site Essen\/D\u00fcsseldorf, D\u00fcsseldorf , Germany"},{"name":"Moorenstra\u00dfe 5, 40225 D\u00fcsseldorf, Germany"}]},{"given":"Jo\u00e3o T","family":"Barata","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa; Av. Prof. Egas Moniz , 1649-028, Lisboa , Portugal"}]},{"given":"Claudia C","family":"Faria","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa; Av. 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