Is fibroblast growth factor receptor 4 a suitable target of cancer therapy?
Fibroblast growth factors (FGF) and their tyrosine kinase receptors (FGFR) support cell proliferation, survival and migration during embryonic development, organogenesis and tissue maintenance and their deregulation is frequently observed in cancer development and progression. Consequently, increasing efforts are focusing on the development of strategies to target FGF/FGFR signaling for cancer therapy. Among the FGFRs the family member FGFR4 is least well understood and differs from FGFRs1-3 in several aspects. Importantly, FGFR4 deletion does not lead to an embryonic lethal phenotype suggesting the possibility that its inhibition in cancer therapy might not cause grave adverse effects. In addition, the FGFR4 kinase domain differs sufficiently from those of FGFRs1-3 to permit development of highly specific inhibitors. The oncogenic impact of FGFR4, however, is not undisputed, as the FGFR4-mediated hormonal effects of several FGF ligands may also constitute a tissue-protective tumor suppressor activity especially in the liver. Therefore it is the purpose of this review to summarize all relevant aspects of FGFR4 physiology and pathophysiology and discuss the options of targeting this receptor for cancer therapy.
Christine
C
Heinzle
Zeynep
Z
Erdem
Jakob
J
Paur
Bettina
B
Grasl-Kraupp
Klaus
K
Holzmann
Michael
M
Grusch
Walter
W
Berger
Institute of Cancer Research, Department of Medicine 1, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria. brigitte.marian@meduniwien.ac.at.
Brigitte
B
Marian
D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D017468:Receptors, Fibroblast Growth Factor; D051499:Receptor, Fibroblast Growth Factor, Type 4