Fibroblast growth factor receptor (FGFR) 3 and 4 as putative targets for the treatment of hepatocellular carcinoma

In hepatocellular carcinoma at least one member of the FGF8 subfamily (FGF8, FGF17, and FGF18) was up-regulated in 59% of the cases studied. We found that these FGFs act as survival factors for cancer cells under stress conditions, stimulate growth of tumor-derived myofibroblasts, and induce the proliferation and tube formation of hepatic endothelial cells. Thus, FGF8, FGF17, and FGF18 support the development and progression of hepatocellular malignancy (Gauglhofer et al., 2011).

FGF8/17/18 are ligands for FGFR3 and/or FGFR4. Therefore, we address the question whether disruption of FGFR3- and/or FGFR4-mediated signalling is a valuable therapeutic option. First data show that dominant negative FGFR3 and FGFR4 constructs impair anchorage-independent growth and tumor formation of hepatocarcinoma cells in SCID mice. 

This project receives funding by the Austrian Science Fund (FWF; P23491).