% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Makhmut:306184,
author = {A. Makhmut and M. P. Dragomir$^*$ and S. Fritzsche and M.
Moebs and W. D. Schmitt and E. T. Taube and F. Coscia},
title = {{S}patial proteomics of ovarian cancer precursors
delineates early disease changes and drug targets.},
journal = {Molecular systems biology},
volume = {22},
number = {1},
issn = {1744-4292},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2025-02424},
pages = {7-41},
year = {2026},
note = {2026 Jan;22(1):7-41},
abstract = {High-grade serous ovarian cancer (HGSOC) is often detected
at an advanced stage, where curative treatment options are
limited. Recent advances in ultrasensitive mass
spectrometry-based spatial proteomics have provided a unique
opportunity to uncover molecular drivers of early
tumorigenesis and novel therapeutic targets. Here, we
present a comprehensive proteomic analysis of serous tubal
intraepithelial carcinoma (STIC), the HGSOC precursor
lesion, and concurrent invasive carcinoma, covering more
than 10,000 proteins from ultra-low input archival tissue.
STIC and HGSOC showed highly similar proteomes, clustering
into two subtypes with distinct tumor-immune
microenvironments and common remodeling of the extracellular
matrix. We discovered cell-of-origin signatures from
secretory fallopian tube epithelial cells in STICs and
identified early dysregulated pathways of therapeutic
relevance. Targeting cholesterol biosynthesis by inhibiting
the terminal steps via DHCR7 showed therapeutic effects in
ovarian cancer cell lines and synergized with
standard-of-care carboplatin treatment. This study
demonstrates the power of spatially resolved quantitative
proteomics in understanding early carcinogenesis and
provides a rich resource for biomarker and drug target
research.},
keywords = {Cancer Proteomics (Other) / High-Grade Serous Ovarian
Cancer (Other) / Serous Tubal Intraepithelial Carcinoma
(Other) / Spatial Tissue Proteomics (Other)},
cin = {BE01},
ddc = {570},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41233595},
doi = {10.1038/s44320-025-00168-4},
url = {https://inrepo02.dkfz.de/record/306184},
}