FGFR3

FGFR3 encodes a receptor tyrosine kinase that acts as a negative regulator of endochondral bone growth by limiting chondrocyte proliferation, hypertrophic differentiation, and osteogenesis in growth plate cartilage^[1][2]. Mechanistically, activated FGFR3 signaling inhibits bone growth through MAPK-dependent suppression of chondrocyte differentiation and STAT1-associated suppression of chondrocyte proliferation^[3]. In skeletal disease models, activating FGFR3 mutations explain achondroplasia as gain-of-function lesions that intensify this inhibitory growth-control program^[1]. In cancer, activating FGFR3 mutations occur in bladder and cervix carcinomas, and FGFR3-TACC3 fusions show oncogenic activity in glioblastoma models^[4][5]. Compared with related isoforms, alternative splicing of the FGFR3 IgIII domain generates IIIb/IIIc variants with distinct ligand-binding properties, and FGFR3 IIIb binds only acidic FGF in the reported binding assays^[6]. For experimental and translational applications, erdafitinib, an FGFR1-4 tyrosine kinase inhibitor, produced clinical activity in advanced urothelial carcinoma with susceptible FGFR2/3 alterations and later improved overall survival versus chemotherapy after anti-PD-1/PD-L1 treatment^[7][8].