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@ARTICLE{Koi:282343,
      author       = {L. Koi and V. Bitto$^*$ and C. Weise and L. Möbius and A.
                      Linge$^*$ and S. Löck$^*$ and A. Yaromina and M. J.
                      Besso$^*$ and C. Valentini and M. Pfeifer and J. Overgaard
                      and D. Zips and I. Kurth$^*$ and M. Krause$^*$ and M.
                      Baumann$^*$},
      title        = {{P}rognostic biomarkers for the response to the
                      radiosensitizer nimorazole combined with {RCT}x: a
                      pre-clinical trial in {HNSCC} xenografts.},
      journal      = {Journal of translational medicine},
      volume       = {21},
      number       = {1},
      issn         = {1479-5876},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-01727},
      pages        = {576},
      year         = {2023},
      note         = {#EA:B330#EA:E220#LA:E220#},
      abstract     = {Tumor hypoxia is associated with resistance to radiotherapy
                      and chemotherapy. In head and neck squamous cell carcinoma
                      (HNSCC), nimorazole, an oxygen mimic, combined with
                      radiotherapy (RT) enabled to improve loco-regional control
                      (LRC) in some patients with hypoxic tumors but it is unknown
                      whether this holds also for radiochemotherapy (RCTx). Here,
                      we investigated the impact of nimorazole combined with RCTx
                      in HNSCC xenografts and explored molecular biomarkers for
                      its targeted use.Irradiations were performed with 30
                      fractions in 6 weeks combined with weekly cisplatin.
                      Nimorazole was applied before each fraction, beginning with
                      the first or after ten fractions. Effect of RCTx with or
                      without addition of nimorazole was quantified as permanent
                      local control after irradiation. For histological evaluation
                      and targeted gene expression analysis, tumors were excised
                      untreated or after ten fractions. Using quantitative image
                      analysis, micromilieu parameters were determined.Nimorazole
                      combined with RCTx significantly improved permanent local
                      control in two tumor models, and showed a potential
                      improvement in two additional models. In these four models,
                      pimonidazole hypoxic volume (pHV) was significantly reduced
                      after ten fractions of RCTx alone. Our results suggest that
                      nimorazole combined with RCTx might improve TCR compared to
                      RCTx alone if hypoxia is decreased during the course of RCTx
                      but further experiments are warranted to verify this
                      association. Differential gene expression analysis revealed
                      12 genes as potential for RCTx response. When evaluated in
                      patients with HNSCC who were treated with primary RCTx,
                      these genes were predictive for LRC.Nimorazole combined with
                      RCTx improved local tumor control in some but not in all
                      HNSCC xenografts. We identified prognostic biomarkers with
                      the potential for translation to patients with HNSCC.},
      keywords     = {Biomarker (Other) / HNSCC (Other) / Hypoxia (Other) /
                      Nimorazole (Other) / Radiochemotherapy (Other) /
                      Radioresistance (Other) / Radiosensitizer (Other) /
                      Radiotherapy (Other)},
      cin          = {B330 / E220 / DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B330-20160331 / I:(DE-He78)E220-20160331 /
                      I:(DE-He78)DD01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37633930},
      doi          = {10.1186/s12967-023-04439-2},
      url          = {https://inrepo02.dkfz.de/record/282343},
}