Characterization of human head and neck squamous cell carcinoma (HNSCC) on a kinomic level

Background:

The biology of HNSCC is characterized by a large heterogeneity. Therefore, individual analysis of HNSCC is of utmost importance for an aspired personalized treatment. For molecular targeting using inhibitors, those kinases, which are hyperactivated in tumors compared to the normal tissue, have to be identified. In a recent kinome profiling study using the PamStation-technology we have identified kinases of the Src-family (SFK) to be highly activated in a significant number of HNSCC. Now we focus on intratumoral heterogeneity, reproducibility of this approach, identification of Src-unrelated kinases and the specific targeting of those.

Methods:

Kinomic profiling of 16 HPV-(-)-HNSCC and corresponding normal tissue was performed using the PamStation®12. The results were validated by Western blot. For functional assays, selected inhibitors and adequately chosen HNSCC cell lines were analyzed.

Results:

In addition to SFK kinases for example of the insulin receptor and ROR-family were identified to be upregulated in several HNSCC samples. Using specific inhibitors on HNSCC cell lines we were able to observe a blockage of the signalling, a reduced proliferation and survival. In repeated testing of the same piece of tumor and by analysing different samples from single tumors we usually detected the same pattern of upregulated kinases without huge variations in signal quality.

Conclusions:

The identification of upregulated kinases by kinome profiling using the PamStation®12 is efficient and reproducible. The intratumoral heterogeneity seemed to have only a minor impact on upstream kinase activity. In addition to SFK we identified several other kinases to be frequently upregulated in HNSCC, representing new potential targets for a personalized molecular therapy.

Publication History

Publication Date:
23 April 2019 (online)