Fibroblast growth factor receptor 1 (FGFR1) (FGFR1)

Fibroblast growth factor receptor 1 (FGFR1) is a receptor tyrosine kinase that serves as a cell-surface receptor for fibroblast growth factors (FGFs), mediating essential processes such as embryonic development, cell proliferation, differentiation, migration, and angiogenesis through downstream pathways including MAPK/ERK, PI3K/AKT, and PLCγ signaling. Upon FGF binding (often with heparin assistance), FGFR1 dimerizes, undergoes autophosphorylation, and activates cascades that regulate mesoderm patterning, skeletogenesis, neuron development, and tissue morphogenesis. Dysregulation via amplification, fusions, or mutations drives oncogenesis in cancers like rhabdomyosarcoma, lung cancer, and breast cancer, where FGFR1 promotes tumor growth, metastasis, and revascularization. Small molecule inhibitors targeting the FGFR1 kinase domain (e.g., by locking inactive DFG-out conformations) have shown efficacy in FGFR-altered tumors, synergizing with anti-angiogenic therapies. Challenges include managing toxicities like hyperphosphatemia from phosphate homeostasis disruption and ensuring selectivity amid FGFR family homology.

Other names

basic fibroblast growth factor receptor 1fms-related tyrosine kinase 2CD331FGFR1b (IIIb isoform)FGFR1c (IIIc isoform)

Inhibition of tyrosine kinase activity (blocks ATP binding and kinase activation via DFG-in/DFG-out conformational changes), prevention of FGFR dimerization and autophosphorylation, suppression of downstream signaling (MAPK/ERK, PI3K/AKT, PLCγ pathways)