guest ::
| Home > Publications database > 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. |
| Home > Publications database > 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. |
| Journal Article | DKFZ-2025-01111 |
; ; ; ; ; ; ; ; ; ; ; ; ;
2025
MDPI
Basel
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.
Keyword(s): Sacituzumab govitecan ; Trop-2 ; kinome ; precision medicine ; recurrent HNSCC ; tumor models ; tumor tissue slices
; 
; 
; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
