Abstract
The fibroblast growth factor receptor (FGFR) signaling pathway has long been known to cancer researchers because of its role in cell survival, proliferation, migration, and angiogenesis. Dysregulation of FGFR signaling is frequently reported in cancer studies, but most of these studies focus on FGFR1-3. However, there is growing evidence implicating an important and unique role of FGFR4 in oncogenesis, tumor progression, and resistance to anti-tumor therapy in multiple types of cancer. Importantly, there are several novel FGFR4-specific inhibitors in clinical trials, making FGFR4 an attractive target for further research. In this review, we focus on assessing the role of FGFR4 in cancer, with an emphasis on breast cancer. First, the structure, physiological functions and downstream signaling pathways of FGFR4 are introduced. Next, different mechanisms reported to cause aberrant FGFR4 activation and their functions in cancer are discussed, including FGFR4 overexpression, FGF ligand overexpression, FGFR4 somatic hotspot mutations, and the FGFR4 G388R single nucleotide polymorphism. Finally, ongoing and recently completed clinical trials targeting FGFRs in cancer are reviewed, highlighting the therapeutic potential of FGFR4 inhibition for the treatment of breast cancer.