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.
