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@ARTICLE{Beumers:285945,
      author       = {L. Beumers$^*$ and E.-I. Vlachavas$^*$ and S. Borgoni$^*$
                      and L. Schwarzmüller$^*$ and L. Penso-Dolfin$^*$ and B.
                      Michels$^*$ and E. Sofyali$^*$ and S. Burmester$^*$ and D.
                      Heiss$^*$ and H. Wilhelm$^*$ and Y. Yarden and D. Helm$^*$
                      and R. Will$^*$ and A. Goncalves$^*$ and S. Wiemann$^*$},
      title        = {{C}lonal heterogeneity in {ER}+ breast cancer reveals the
                      proteasome and {PKC} as potential therapeutic targets.},
      journal      = {npj Breast cancer},
      volume       = {9},
      number       = {1},
      issn         = {2374-4677},
      address      = {London},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2023-02535},
      pages        = {97},
      year         = {2023},
      note         = {#EA:B050#LA:B050#},
      abstract     = {Intratumoral heterogeneity impacts the success or failure
                      of anti-cancer therapies. Here, we investigated the
                      evolution and mechanistic heterogeneity in clonal
                      populations of cell models for estrogen receptor positive
                      breast cancer. To this end, we established barcoded models
                      of luminal breast cancer and rendered them resistant to
                      commonly applied first line endocrine therapies. By
                      isolating single clones from the resistant cell pools and
                      characterizing replicates of individual clones we observed
                      inter- (between cell lines) and intra-tumor (between
                      different clones from the same cell line) heterogeneity.
                      Molecular characterization at RNA and phospho-proteomic
                      levels revealed private clonal activation of the unfolded
                      protein response and respective sensitivity to inhibition of
                      the proteasome, and potentially shared sensitivities for
                      repression of protein kinase C. Our in vitro findings are
                      consistent with tumor-heterogeneity that is observed in
                      breast cancer patients thus highlighting the need to uncover
                      heterogeneity at an individual patient level and to adjust
                      therapies accordingly.},
      cin          = {B050 / B210 / W120 / W111},
      ddc          = {610},
      cid          = {I:(DE-He78)B050-20160331 / I:(DE-He78)B210-20160331 /
                      I:(DE-He78)W120-20160331 / I:(DE-He78)W111-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38042915},
      pmc          = {pmc:PMC10693625},
      doi          = {10.1038/s41523-023-00604-4},
      url          = {https://inrepo02.dkfz.de/record/285945},
}