Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor (FGFR) complex (FGF2-FGFR complex)

Basic fibroblast growth factor (FGF2), also known as bFGF, is a pleiotropic cytokine that plays a fundamental role in cell growth, survival, and differentiation by signaling through its high-affinity receptor tyrosine kinases, specifically FGFR1, FGFR2, FGFR3, and FGFR4 (Source: NIH, 2021). The formation of a functional signaling complex requires the presence of heparan sulfate proteoglycans (HSPGs), which stabilize the FGF2-FGFR interaction and facilitate receptor dimerization and subsequent intracellular kinase activation (Source: WJG, 2016). This pathway is critical for physiological processes such as angiogenesis, wound healing, and embryonic development, but its dysregulation is a major driver in many human cancers, including cholangiocarcinoma, urothelial carcinoma, and breast cancer (Source: Nature Reviews Clinical Oncology, 2018). Therapeutic targeting of the FGF2-FGFR complex involves small-molecule tyrosine kinase inhibitors (TKIs) that block the intracellular ATP-binding site, as well as monoclonal antibodies and ligand traps that interfere with extracellular binding (Source: MDPI, 2020). Clinical use of these inhibitors is often associated with specific toxicities, most notably hyperphosphatemia due to the inhibition of FGF23 signaling, and the emergence of gatekeeper mutations that confer drug resistance (Source: PubMed, 2024).

Other names

Basic fibroblast growth factorbFGFFGF-2Heparin-binding growth factor 2HBGF-2ProstatropinFGF2-FGFR-HSPG complexFibroblast growth factor receptor complex

Inhibition of the ATP-binding site of the FGFR kinase domain, sequestration of FGF ligands via ligand traps, and blocking of ligand-receptor interaction using monoclonal antibodies or aptamers.