Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets
Beteiligte Einrichtungen
- Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde
- Klinik und Poliklinik für Strahlentherapie und Radioonkologie
- Institut für Pathologie
- University Cancer Center Hamburg (UCCH)
- Institut für Anatomie und Experimentelle Morphologie
- Klinik und Poliklinik für Pädiatrische Hämatologie und Onkologie
- Klinik und Poliklinik für Kardiologie
Abstract
Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients. Here we present a systematic analysis of the tyrosine kinases in head and neck cancer using such a test-functional kinome profiling. We detected increased tyrosine kinase activity in tumors compared with their corresponding normal tissue. Moreover, we identified members of the family of Src kinases (Src family kinases [SFK]) to be aberrantly activated in the majority of the tumors, which was confirmed by additional methods. We could also show that SFK hyperphosphorylation is associated with poor prognosis, while inhibition of SFK impaired cell proliferation, especially in cells with hyperactive SFK. In summary, functional kinome profiling identified SFK to be frequently hyperactivated in head and neck squamous cell carcinoma. SFK may therefore be potential therapeutic targets. These results furthermore demonstrate how functional tests help to increase our understanding of cancer biology and support the expansion of precision oncology.
Bibliografische Daten
Originalsprache | Englisch |
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ISSN | 0020-7136 |
DOIs | |
Status | Veröffentlicht - 01.09.2021 |
Anmerkungen des Dekanats
https://doi.org/10.1002/ijc.33606