biostudies-literaturePaisana EFundação para a Ciência e a Tecnologiavdad048https://www.ebi.ac.uk/biostudies/studies/S-EPMC10195208biostudies-literatureUnknown5(1)<h4>Background</h4>Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies.<h4>Methods</h4>Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of <i>UBE2C</i>, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins.<h4>Results</h4>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 PNeuro-oncology advancesUBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease.PMC10195208PD/BD/128288/2017PTDC/MEDONC/Roque RQin NPicard DCascao RPauck DDoutel DPimentel JRuivo PRemke MBarreto CPaisana ECabecadas JCustodia CMiguens JFaria CCCarvalho TBarata JTfalseUBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease.<h4>Background</h4>Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies.<h4>Methods</h4>Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of <i>UBE2C</i>, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins.<h4>Results</h4>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 P2023-01-01T00:00:00Z2023 Jan-Dec2026-05-28T22:59:55.615Z2025-04-04T23:44:41.208ZS-EPMC101952083721595410.1093/noajnl/vdad048