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@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},
}