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@ARTICLE{Issing:299559,
      author       = {C. Issing$^*$ and C. Menche$^*$ and M. R. Richter and M. H.
                      Mosa and J. von der Grün and M. Fleischmann$^*$ and P.
                      Thoenissen and R. Winkelmann and T. Darvishi and A. G. Loth
                      and S. Ghanaati and F. Rödel$^*$ and P. J. Wild and C. H.
                      Brandts$^*$ and T. Stöver and H. F. Farin$^*$},
      title        = {{H}ead and neck tumor organoid biobank for modelling
                      individual responses to radiation therapy according to the
                      {TP}53/{HPV} status.},
      journal      = {Journal of experimental $\&$ clinical cancer research},
      volume       = {44},
      number       = {1},
      issn         = {0392-9078},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2025-00503},
      pages        = {85},
      year         = {2025},
      abstract     = {Head and neck cancers (HNC) represent an extremely
                      heterogeneous group of diseases with a poorly predictable
                      therapy outcome. Patient-derived tumor organoids (PDTO)
                      offer enormous potential for individualized therapy testing
                      and a better mechanistic understanding of the main HNC
                      drivers.Here, we have established a comprehensive
                      molecularly and functionally characterized head and neck
                      organoid biobank (HNOB) recapitulating the clinically
                      relevant subtypes of TP53 mutant and human papillomavirus
                      type 16 (HPV 16) infection-driven HNC. Organoids were
                      exposed to radiotherapy, and responses were correlated with
                      clinical data. Genetically engineered normal and tumor
                      organoids were used for testing the direct functional
                      consequences of TP53-loss and HPV infection.The HNOB
                      consisting of 18 organoid models, including 15 tumor models,
                      was generated. We identified subtype-associated
                      transcriptomic signatures and pathological features,
                      including sensitivity to TP53 stabilization by the MDM2
                      inhibitor Nutlin-3. Furthermore, we describe an in vitro
                      radio response assay revealing phenotypic heterogeneity
                      linked to the individual patient's treatment outcome,
                      including relapse probability. Using genetically engineered
                      organoids, the possibility of co-existence of both cancer
                      drivers was confirmed. TP53 loss, as well as HPV, increased
                      growth in normal and tumor organoids. TP53 loss-of-function
                      alone was insufficient to promote radiation resistance,
                      whereas HPV 16 oncogenes E6/E7 mediated radiosensitivity via
                      induction of cell cycle arrest.Our results highlight the
                      translational value of the head and neck organoid models not
                      only for patient stratification but also for mechanistic
                      validation of therapy responsiveness of specific cancer
                      drivers.},
      keywords     = {Humans / Tumor Suppressor Protein p53: metabolism / Tumor
                      Suppressor Protein p53: genetics / Head and Neck Neoplasms:
                      radiotherapy / Head and Neck Neoplasms: virology / Head and
                      Neck Neoplasms: pathology / Head and Neck Neoplasms:
                      genetics / Organoids: virology / Biological Specimen Banks /
                      Papillomavirus Infections: virology / Papillomavirus
                      Infections: complications / Papillomavirus Infections:
                      radiotherapy / Female / Male / CRISPR/Cas9 (Other) / Genetic
                      editing (Other) / Head and neck squamous cell carcinoma
                      (Other) / In vitro therapy testing (Other) / Preclinical
                      model (Other) / Radioresistance (Other) / Tumor organoid
                      biobank (Other) / Tumor Suppressor Protein p53 (NLM
                      Chemicals) / TP53 protein, human (NLM Chemicals)},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40045309},
      pmc          = {pmc:PMC11881459},
      doi          = {10.1186/s13046-025-03345-3},
      url          = {https://inrepo02.dkfz.de/record/299559},
}