%0 Journal Article
%A Zech, Henrike Barbara
%A Schafhausen, Philippe
%A Ramke, Leonie
%A Velthaus, Janna-Lisa
%A Kreutzfeldt, Simon
%A Hübschmann, Daniel
%A Rothkamm, Kai
%A Bokemeyer, Carsten
%A Hoffmann, Anna Sophie
%A Fröhling, Stefan
%A Glimm, Hanno
%A Betz, Christian Stephan
%A Kriegs, Malte
%A Christopeit, Maximilian
%T Last Resort? Rationale for Comprehensive Molecular Analysis in Treatment-Refractory R/M HNSCC: A Case Report of Remarkable Response to Sacituzumab Govitecan Following Molecular and Functional Characterization.
%J Biomedicines
%V 13
%N 5
%@ 2227-9059
%C Basel
%I MDPI
%M DKFZ-2025-01111
%P 1266
%D 2025
%X 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
%K Sacituzumab govitecan (Other)
%K Trop-2 (Other)
%K kinome (Other)
%K precision medicine (Other)
%K recurrent HNSCC (Other)
%K tumor models (Other)
%K tumor tissue slices (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40427091
%2 pmc:PMC12108840
%R 10.3390/biomedicines13051266
%U https://inrepo02.dkfz.de/record/301719