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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

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 the...

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Autori principali: Zech, Henrike Barbara Antonia Angelika (Autore) , Schafhausen, Philippe (Autore) , Ramke, Leonie (Autore) , Velthaus, Janna-Lisa (Autore) , Kreutzfeldt, Simon (Autore) , Hübschmann, Daniel (Autore) , Rothkamm, Kai (Autore) , Bokemeyer, Carsten (Autore) , Hoffmann, Anna Sophie (Autore) , Fröhling, Stefan (Autore) , Glimm, Hanno (Autore) , Betz, Christian Stephan (Autore) , Kriegs, Malte (Autore) , Christopeit, Maximilian (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 21 May 2025
In: Biomedicines
Year: 2025, Volume: 13, Fascicolo: 5, Pages: 1-13
ISSN:2227-9059
DOI:10.3390/biomedicines13051266
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/biomedicines13051266
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2227-9059/13/5/1266
Testo
Note sull'autore:Henrike Barbara Zech, Philippe Schafhausen, Leonie Ramke, Janna-Lisa Velthaus, Simon Kreutzfeldt, Daniel Hübschmann, Kai Rothkamm, Carsten Bokemeyer, Anna Sophie Hoffmann, Stefan Fröhling, Hanno Glimm, Christian Stephan Betz, Malte Kriegs and Maximilian Christopeit
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Riassunto: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.
Descrizione del documento:Gesehen am 02.06.2026
Descrizione fisica:Online Resource
ISSN:2227-9059
DOI:10.3390/biomedicines13051266

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