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@ARTICLE{Spartalis:143834,
      author       = {C. Spartalis and E. M. Schmidt and M. Elmasry and G. B.
                      Schulz and T. Kirchner$^*$ and D. Horst$^*$},
      title        = {{I}n vivo effects of chemotherapy on oncogenic pathways in
                      colorectal cancer.},
      journal      = {Cancer science},
      volume       = {110},
      number       = {8},
      issn         = {1349-7006},
      address      = {Tokyo},
      publisher    = {Assoc.},
      reportid     = {DKFZ-2019-01396},
      pages        = {2529-2539},
      year         = {2019},
      abstract     = {Patients with advanced colorectal cancer often are treated
                      with systemic cytotoxic therapy using fluouracil (5-FU),
                      oxaliplatin, irinotecan, and FOLFOX or FOLFIRI combination
                      protocols. Additionally, signaling pathways that are active
                      in colorectal cancer can be therapeutically targeted. Here,
                      we examined if chemotherapy impacts on WNT, MAPK and NOTCH
                      signaling pathways in xenograft models of colon cancer.
                      Furthermore, we tested if combining chemotherapy with MAPK
                      and NOTCH inhibition has superior therapeutic effects. We
                      demonstrate that tumor cells with high WNT, MAPK and NOTCH
                      activity are variably affected by different chemotherapeutic
                      regimens, while vital tumor cells with different pathway
                      activity remain in treated colon cancer xenografts. Although
                      this provided a rationale to additionally target pathway
                      activity, we found no significant increase in therapy
                      response when combining MAPK and NOTCH inhibition with
                      fluouracil chemotherapy. We attribute this finding to a
                      decrease in tumor cell proliferation upon MAPK and NOTCH
                      inhibition, resulting in reduced effectiveness of cytotoxic
                      treatment. Therapeutic benefits of combining chemotherapy
                      with targeting of signaling pathways that are active in
                      colon cancer thus must be critically evaluated for patients
                      with colorectal cancer. This article is protected by
                      copyright. All rights reserved.},
      cin          = {E131 / L101 / L201},
      ddc          = {610},
      cid          = {I:(DE-He78)E131-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)L201-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31119819},
      doi          = {10.1111/cas.14077},
      url          = {https://inrepo02.dkfz.de/record/143834},
}