Abstract (eng)
Overexpression of FGFR4 and/or its stimulating ligands has been observed for various tumor types. Recently, the SNP G388R of FGFR4 has moved into the focus of interest as both allelic forms seem to play important roles in tumorigenesis. So far, inhibitory strategies for FGFR4 are limited, mainly because available drugs were initially designed to block other RTK and lack specificity for FGFR4. In this study, we were able to show the inhibitory potential of the TKI PD173074 towards Ba/F3 cells expressing only FGFR4. Using the same cell line, we evaluated blockade of FGFR4 via infection with adenoviral constructs. Treatment with the dn4 construct resulted in decreased viability, indicating successful inhibition. In addition, both dn4 and sol4 altered signaling pathways of FGFR4 expressing Ba/F3 cells. Moreover, we performed in vivo experiments using three CRC cell lines with varying FGFR4 expression and allelotype. Tumor growth rates for these xenografts were decreased compared to control, whereby efficiency of inhibition varied between the cell lines. This indicates, that blockade of FGFR4 could play an important role in cancer therapy of patients with altered FGFR4 background.