Tyrosine kinase inhibitors in head and neck squamous cell carcinoma – a therapeutic chance?

Introduction Tyrosine kinase inhibitors (TKI) don`t improve the outcome in head and neck squamous cell carcinoma (HNSCC). The only substance used in HNSCC is the antibody Cetuximab, which is directed against Epidermal Growth Factor Receptor (EGFR). EGFR is a transmembrane receptor with intrinsic tyrosine kinase activity. It is our goal to improve the understanding of mechanisms of resistance and therapeutic effects of TKI in HNSCC.

Material/Methods HNSCC cell lines were tested regarding their EGRF expression by Western Blot (e.g. UMSCC-11A, UMSCC-11B). Following the effectivity of TKI (e.g. Lapatinib, Afatinib) was investigated in 2D- and 3D-cell culture by FACS-analysis and determination of IC50 in a Cell Viability Assay.

Results We could evaluate the effect of TKI in the cell lines mentioned in 2D- as well as in 3D-cell culture. Cytotoxic effects could be found by Afatinib and Lapatinib on UMSCC-11A and UMSCC-22B in 2D-cell culture. Outstandingly in 3D-cell culture Lapatinib showed a very limited effectiveness (IC 50 in UMSCC-11B >50µM).

Conclusion Former findings describe the therapeutic effect of TKI in HNSCC in combination e.g. with platin in 2D-cell culture. In our opinion 3D-cell culture is superior to 2D-cell culture when it comes to evaluation of therapeutic potency because the physiological cell architecture in vivo is presented in a better way. The transfer to more physiological cell culture models could help to better understand the real conditions in HNSCC and to identify new therapeutic chances. In 3D-cell culture we could show limited effectiveness of Lapatinib in UMSCC-11B. Here evaluation of downstream-mechanisms could help to identify options to improve potency of TKI in HNSCC.

Poster-PDF A-1267.pdf

Conflict of interest

Der Erstautor gibt keinen Interessenskonflikt an.

Publication History

Article published online:
13 May 2021