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@ARTICLE{Zech:301719,
      author       = {H. B. Zech and P. Schafhausen and L. Ramke and J.-L.
                      Velthaus and S. Kreutzfeldt$^*$ and D. Hübschmann$^*$ and
                      K. Rothkamm and C. Bokemeyer and A. S. Hoffmann and S.
                      Fröhling$^*$ and H. Glimm$^*$ and C. S. Betz and M. Kriegs
                      and M. Christopeit},
      title        = {{L}ast {R}esort? {R}ationale for {C}omprehensive
                      {M}olecular {A}nalysis in {T}reatment-{R}efractory {R}/{M}
                      {HNSCC}: {A} {C}ase {R}eport of {R}emarkable {R}esponse to
                      {S}acituzumab {G}ovitecan {F}ollowing {M}olecular and
                      {F}unctional {C}haracterization.},
      journal      = {Biomedicines},
      volume       = {13},
      number       = {5},
      issn         = {2227-9059},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2025-01111},
      pages        = {1266},
      year         = {2025},
      abstract     = {Background/Objectives: In recurrent/metastatic head and
                      neck squamous cell carcinoma (R/M HNSCC), the overall
                      prognosis is poor, and systemic treatment options remain
                      limited. While precision therapy approaches have
                      revolutionized treatment strategies in several tumor types,
                      molecularly informed therapies in R/M HNSCC are rare,
                      primarily due to the low number of actionable genetic
                      alterations identified through next-generation sequencing
                      (NGS) panels. There is an urgent need to establish precision
                      therapy approaches in R/M HNSCC using innovative predictive
                      testing. Methods: We report the case of a 43-year-old
                      patient with recurrent oral cancer who was extensively
                      pretreated and comprehensively characterized using both
                      descriptive and functional testing. Results: NGS revealed no
                      targetable alterations. A tumor tissue slice
                      radiosensitivity assay suggested radioresistance, arguing
                      against re-irradiation. Kinome profiling identified
                      upregulated Src-family kinases (SFK), and SFK inhibition
                      reduced kinase activity in vitro. Most notably, mRNA
                      analysis demonstrated high Trop-2 overexpression, confirmed
                      by immunohistochemistry (3+ in $100\%$ of tumor cells).
                      Following six cycles of the Trop-2-directed antibody-drug
                      conjugate Sacituzumab govitecan (SG), the patient had an
                      impressive clinical response. Conclusions: Tumor
                      characterization beyond genetic profiling can identify novel
                      treatment options in therapy-refractory HNSCC. This is the
                      first report of 'real-world' data on promising antitumor
                      efficacy of SG in a heavily pretreated oral cancer patient
                      with Trop-2 overexpression. Consistent with the findings of
                      the Basket TROPiCS-03 study, SG appears to be a promising
                      novel therapy option for R/M HNSCC after failure of
                      immunotherapy and chemotherapy, particularly in patients
                      with Trop-2 overexpression.},
      keywords     = {Sacituzumab govitecan (Other) / Trop-2 (Other) / kinome
                      (Other) / precision medicine (Other) / recurrent HNSCC
                      (Other) / tumor models (Other) / tumor tissue slices
                      (Other)},
      cin          = {B340 / HD01 / DD01},
      ddc          = {570},
      cid          = {I:(DE-He78)B340-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)DD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40427091},
      pmc          = {pmc:PMC12108840},
      doi          = {10.3390/biomedicines13051266},
      url          = {https://inrepo02.dkfz.de/record/301719},
}