TY  - JOUR
AU  - Zech, Henrike Barbara
AU  - Schafhausen, Philippe
AU  - Ramke, Leonie
AU  - Velthaus, Janna-Lisa
AU  - Kreutzfeldt, Simon
AU  - Hübschmann, Daniel
AU  - Rothkamm, Kai
AU  - Bokemeyer, Carsten
AU  - Hoffmann, Anna Sophie
AU  - Fröhling, Stefan
AU  - Glimm, Hanno
AU  - Betz, Christian Stephan
AU  - Kriegs, Malte
AU  - Christopeit, Maximilian
TI  - 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.
JO  - Biomedicines
VL  - 13
IS  - 5
SN  - 2227-9059
CY  - Basel
PB  - MDPI
M1  - DKFZ-2025-01111
SP  - 1266
PY  - 2025
AB  - 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
KW  - Sacituzumab govitecan (Other)
KW  - Trop-2 (Other)
KW  - kinome (Other)
KW  - precision medicine (Other)
KW  - recurrent HNSCC (Other)
KW  - tumor models (Other)
KW  - tumor tissue slices (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40427091
C2  - pmc:PMC12108840
DO  - DOI:10.3390/biomedicines13051266
UR  - https://inrepo02.dkfz.de/record/301719
ER  -