Fibroblast growth factor receptor 1-4 (FGFR1-4)

Fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, and FGFR4) are a family of transmembrane receptor tyrosine kinases that play critical roles in cellular signaling pathways (UniProt P11362, P21802). Upon binding to fibroblast growth factor (FGF) ligands and heparin sulfate proteoglycans, these receptors undergo dimerization and trans-phosphorylation, activating downstream cascades such as MAPK/ERK, PI3K/AKT, and PLCγ (Korc & Friesel, 2009, PMID: 19242484). These pathways are essential for normal physiological processes including embryonic development, tissue repair, and angiogenesis. Dysregulation of FGFR signaling through gene amplification, point mutations, or chromosomal translocations is a frequent driver in various malignancies, including urothelial carcinoma and cholangiocarcinoma (Katoh, 2019, PMID: 30710159). Consequently, FGFRs have become significant therapeutic targets, with several small-molecule tyrosine kinase inhibitors and monoclonal antibodies approved or in clinical development (FDA, 2023). Therapeutic intervention aims to block aberrant signaling to inhibit tumor growth and survival, though management of off-target effects like hyperphosphatemia, caused by FGFR1 inhibition in the kidney, remains a clinical challenge (Chae et al., 2017, PMID: 28110339).

Other names

FGFR familyCD331/CD332/CD333/CD334Receptor tyrosine protein kinase FGFRFGF receptor

Competitive inhibition of the adenosine triphosphate (ATP) binding site within the intracellular tyrosine kinase domain of FGFR1, 2, 3, and 4, or monoclonal antibody-mediated blockade of ligand binding to the extracellular domain (Katoh, 2019, PMID: 30710159; FDA, 2023).