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@ARTICLE{Gatzweiler:178967,
      author       = {C. Gatzweiler$^*$ and J. Ridinger$^*$ and S. Herter$^*$ and
                      X. F. Gerloff$^*$ and D. ElHarouni$^*$ and Y. Berker$^*$ and
                      R. Imle$^*$ and L. Schmitt$^*$ and S. Kreth$^*$ and S.
                      Stainczyk$^*$ and S. Ayhan$^*$ and S. Najafi$^*$ and D.
                      Krunic$^*$ and K. Frese and B. Meder and D. Reuss$^*$ and P.
                      Fiesel$^*$ and K. Schramm$^*$ and M. Blattner-Johnson$^*$
                      and D. T. W. Jones$^*$ and A. Banito$^*$ and F.
                      Westermann$^*$ and S. Oppermann$^*$ and T. Milde$^*$ and H.
                      Peterziel$^*$ and O. Witt$^*$ and I. Oehme$^*$},
      title        = {{F}unctional {T}herapeutic {T}arget {V}alidation {U}sing
                      {P}ediatric {Z}ebrafish {X}enograft {M}odels.},
      journal      = {Cancers},
      volume       = {14},
      number       = {3},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2022-00383},
      pages        = {849},
      year         = {2022},
      note         = {#EA:B310#LA:B310#},
      abstract     = {The survival rate among children with relapsed tumors
                      remains poor, due to tumor heterogeneity, lack of directly
                      actionable tumor drivers and multidrug resistance. Novel
                      personalized medicine approaches tailored to each tumor are
                      urgently needed to improve cancer treatment. Current
                      pediatric precision oncology platforms, such as the INFORM
                      (INdividualized Therapy FOr Relapsed Malignancies in
                      Childhood) study, reveal that molecular profiling of tumor
                      tissue identifies targets associated with clinical benefit
                      in a subgroup of patients only and should be complemented
                      with functional drug testing. In such an approach,
                      patient-derived tumor cells are exposed to a library of
                      approved oncological drugs in a physiological setting, e.g.,
                      in the form of animal avatars injected with patient tumor
                      cells. We used molecularly fully characterized tumor samples
                      from the INFORM study to compare drug screen results of
                      individual patient-derived cell models in functional assays:
                      (i) patient-derived spheroid cultures within a few days
                      after tumor dissociation; (ii) tumor cells reisolated from
                      the corresponding mouse PDX; (iii) corresponding long-term
                      organoid-like cultures and (iv) drug evaluation with the
                      corresponding zebrafish PDX (zPDX) model. Each model had its
                      advantage and complemented the others for drug hit and drug
                      combination selection. Our results provide evidence that in
                      vivo zPDX drug screening is a promising add-on to current
                      functional drug screening in precision medicine platforms.},
      keywords     = {drug screen (Other) / functional precision oncology (Other)
                      / mPDX (Other) / patient-derived spheroid culture (Other) /
                      small molecule inhibitors (Other) / targeted therapy (Other)
                      / zPDX (Other)},
      cin          = {B310 / HD01 / B240 / B062 / B380 / B087 / W210 / B300 /
                      B360},
      ddc          = {610},
      cid          = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B240-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)B380-20160331 / I:(DE-He78)B087-20160331 /
                      I:(DE-He78)W210-20160331 / I:(DE-He78)B300-20160331 /
                      I:(DE-He78)B360-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35159116},
      pmc          = {pmc:PMC8834194},
      doi          = {10.3390/cancers14030849},
      url          = {https://inrepo02.dkfz.de/record/178967},
}