Fibroblast growth factor 2–Fibroblast growth factor receptor 1 complex (FGF2–FGFR1 complex)

The Fibroblast growth factor 2–Fibroblast growth factor receptor 1 (FGF2–FGFR1) complex is a signaling assembly formed by the binding of the paracrine ligand FGF2 (basic fibroblast growth factor) to the FGFR1 receptor. This interaction is typically mediated by heparan sulfate proteoglycans (HSPGs), which stabilize the ternary complex and facilitate receptor dimerization [6, 15]. Upon activation, the complex triggers intracellular signaling through the MAPK/ERK, PI3K/AKT, and PLCγ pathways, which are vital for cell proliferation, angiogenesis, and tissue repair [5, 9, 19]. In many cancers, such as squamous non-small cell lung cancer and certain breast cancers, the complex is aberrantly activated due to FGFR1 amplification or FGF2 overexpression, promoting tumor growth and resistance to therapy [1, 14, 15]. Therapeutic interventions include small-molecule tyrosine kinase inhibitors (TKIs) like erdafitinib and pemigatinib, which target the receptor's kinase activity, and novel agents like aptamers or antibodies that disrupt the extracellular ligand-receptor interaction [14, 22]. Managing these therapies requires monitoring for on-target side effects, most notably hyperphosphatemia, which results from FGFR1 inhibition in the kidneys [2, 12].

Other names

Basic fibroblast growth factor–FGFR1 complexbFGF–FGFR1 complexFGF2–FGFR1–HSPG complexFGF2–FGFR1–Heparin complex

Inhibition of receptor tyrosine kinase activity, blocking ligand binding, preventing receptor dimerization, and disrupting ternary complex formation with heparan sulfate proteoglycans.