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| Home > Publications database > UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease. |
| Home > Publications database > UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease. |
| Journal Article | DKFZ-2023-01025 |
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2023
Oxford University Press
Oxford
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Please use a persistent id in citations: doi:10.1093/noajnl/vdad048
Abstract: Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies.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.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.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.
Keyword(s): PI3K/mTOR inhibition ; UBE2C ; brain metastases ; leptomeningeal dissemination
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