Head and neck cancers are a heterogeneous group of tumours of which around 90% are squamous cell carcinomas (HNSCC). Due to limited treatment options and a high recurrence rate in advanced stages, tumour-related mortality is up to 40 – 50%. The purpose of our study is i) establishing new treatment possibilities of HNSCC by addressing different cellular pathways in human tumour cells via a set of small molecule inhibitors and ii) the identification of molecular biomarkers that predict the response to these treatments.
Several growth stimulating pathways have been shown to interfere with the formation of HNSCC, like the WNT or the Hepatocyte growth factor (HGF) related signalling involving the MET receptor. In pilot experiments, we screened 32 cell lines from human HNSCC for noticeable activations of these pathways or downstream interaction partners like MLL. Spheroid grown cancer stem cell-like cells of selected cell lines were treated with inhibitors of WNT signalling (ICG-001, β-catenin-CBP interaction), of the MLL-MENIN interaction (MI2 – 2) or of the MET receptor (PHA 665752). Their viability served as a read out.
Our initial results indicate an interesting inverse correlation between strongly overactivated pathways and their response to treatment: The HNSCC UM-104 cell line for example exhibited a high MET related signalling but no sensitivity for PHA 665752. Likewise, the HNSCC UT-06B cell line, which showed a high WNT related signalling but only marginal response to ICG-001. However, both cell lines responded well to treatments of the other pathways.
The transfer of such findings to primary tumour material in combination with molecular screenings for correlated biomarkers should allow for the design of personalised therapies in head and neck cancers.
