Fibroblast growth factor receptor 3 (FGFR3) isoform IIIc (FGFR3-IIIc)

Fibroblast growth factor receptor 3 (FGFR3) isoform IIIc is a member of the receptor tyrosine kinase family that plays a pivotal role in bone development and cellular homeostasis [1, 2]. This specific isoform is generated by alternative splicing of the third immunoglobulin-like domain, where the inclusion of exon 9 (IIIc) confers high affinity for ligands such as FGF1, FGF2, and FGF8 [2, 3]. While the IIIb isoform is typically restricted to epithelial cells, the IIIc isoform is expressed in mesenchymal tissues and is frequently implicated in the progression of various malignancies through the epithelial-mesenchymal transition [3, 5]. Activating mutations or gene fusions involving FGFR3-IIIc lead to constitutive signaling, driving diseases such as urothelial carcinoma, multiple myeloma, and skeletal dysplasias like achondroplasia [1, 4]. Pharmacological targeting of this receptor primarily involves small-molecule inhibitors that compete for the ATP-binding site of the kinase domain or monoclonal antibodies that interfere with ligand binding [4, 6]. Clinical use of these inhibitors requires careful monitoring for class-specific toxicities, most notably hyperphosphatemia and ocular complications [4, 6].

Other names

FGFR3cFGFR3 isoform 1CD333ACHCEK2JTK4

Inhibition of the intracellular tyrosine kinase domain or prevention of ligand binding and receptor dimerization to block downstream signaling pathways such as MAPK/ERK and PI3K/AKT.