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@ARTICLE{Gengenbacher:164197,
      author       = {N. Gengenbacher$^*$ and M. Singhal$^*$ and C. Mogler and L.
                      Hai$^*$ and L. Milde$^*$ and A. A. Abdul Pari$^*$ and E.
                      Besemfelder$^*$ and C. Fricke$^*$ and D. Baumann$^*$ and S.
                      Gehrs$^*$ and J. Utikal$^*$ and M. Felcht and J. Hu and M.
                      Schlesner$^*$ and R. Offringa$^*$ and S. Chintharlapalli and
                      H. Augustin$^*$},
      title        = {{T}imed {A}ng2-targeted therapy identifies the
                      {A}ngiopoietin-{T}ie pathway as key regulator of fatal
                      lymphogenous metastasis.},
      journal      = {Cancer discovery},
      volume       = {11},
      number       = {2},
      issn         = {2159-8290},
      address      = {Philadelphia, Pa.},
      reportid     = {DKFZ-2020-02307},
      pages        = {424-445},
      year         = {2021},
      note         = {DKFZ-ZMBH Alliance#EA:A190#LA:A190#2021 Feb;11(2):424-445},
      abstract     = {Recent clinical and preclinical advances have highlighted
                      the existence of a previously hypothesized lymphogenous
                      route of metastasis. However, due to a lack of suitable
                      preclinical modeling tools, its contribution to long-term
                      disease outcome and relevance for therapy remain
                      controversial. Here, we established a GEMM fragment-based
                      tumor model uniquely sustaining a functional network of
                      intratumoral lymphatics that facilitates seeding of fatal
                      peripheral metastases. Multi-regimen survival studies and
                      correlative patient data identified primary tumor-derived
                      Angiopoietin-2 (Ang2) as a potent therapeutic target to
                      restrict lymphogenous tumor cell dissemination.
                      Mechanistically, tumor-associated lymphatic endothelial
                      cells (EC), in contrast to blood vascular EC, were found to
                      be critically addicted to the Angiopoietin-Tie pathway.
                      Genetic manipulation experiments in combination with
                      single-cell mapping revealed agonistically-acting
                      Ang2/Tie2-signaling as key regulator of lymphatic
                      maintenance. Correspondingly, acute pre-surgical
                      Ang2-neutralization was sufficient to prolong survival by
                      regressing established intratumoral lymphatics, hence
                      identifying a novel therapeutic regimen that warrants
                      further clinical evaluation.},
      cin          = {A190 / B240 / D200 / A370},
      ddc          = {610},
      cid          = {I:(DE-He78)A190-20160331 / I:(DE-He78)B240-20160331 /
                      I:(DE-He78)D200-20160331 / I:(DE-He78)A370-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33106316},
      doi          = {10.1158/2159-8290.CD-20-0122},
      url          = {https://inrepo02.dkfz.de/record/164197},
}