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@ARTICLE{Paisana:276213,
author = {E. Paisana and R. Cascão and C. Custódia and N. Qin$^*$
and D. Picard$^*$ and D. Pauck$^*$ and T. Carvalho and P.
Ruivo and C. Barreto and D. Doutel and J. Cabeçadas and R.
Roque and J. Pimentel and J. Miguéns and M. Remke$^*$ and
J. T. Barata and C. C. Faria},
title = {{UBE}2{C} promotes leptomeningeal dissemination and is a
therapeutic target in brain metastatic disease.},
journal = {Neuro-oncology advances},
volume = {5},
number = {1},
issn = {2632-2498},
address = {Oxford},
publisher = {Oxford University Press},
reportid = {DKFZ-2023-01025},
pages = {vdad048},
year = {2023},
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.},
keywords = {PI3K/mTOR inhibition (Other) / UBE2C (Other) / brain
metastases (Other) / leptomeningeal dissemination (Other)},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37215954},
pmc = {pmc:PMC10195208},
doi = {10.1093/noajnl/vdad048},
url = {https://inrepo02.dkfz.de/record/276213},
}