Fibroblast growth factor (FGF) (FGF)

Fibroblast growth factors (FGFs) are a large family of signaling proteins, with the mitogenic (paracrine) members playing essential roles in cell proliferation, survival, and differentiation during development and adult tissue homeostasis (Ornitz & Itoh, 2015). These ligands, such as FGF1, FGF2, and FGF7, bind to cell-surface fibroblast growth factor receptors (FGFRs) in the presence of heparin or heparan sulfate proteoglycans to initiate intracellular signaling cascades like the MAPK/ERK and PI3K/Akt pathways (Turner & Grose, 2010). Dysregulation of these mitogenic ligands, often through autocrine or paracrine overexpression, is a hallmark of various malignancies, where they drive tumor growth, angiogenesis, and resistance to chemotherapy (Katoh, 2016). Therapeutic strategies targeting this system include the use of "FGF traps" like FP-1039, which sequester ligands to prevent receptor activation, as well as small-molecule tyrosine kinase inhibitors like erdafitinib and pemigatinib that block the downstream effects of ligand binding (Dieci et al., 2013). Beyond oncology, mitogenic FGFs are involved in wound healing and cardiovascular repair, though their systemic inhibition can lead to side effects such as hyperphosphatemia and ocular toxicities due to off-target effects on endocrine FGF signaling (Kroening et al., 2022).

Other names

Mitogenic fibroblast growth factorHeparin-binding growth factorHBGFParacrine fibroblast growth factor

Inhibition of the fibroblast growth factor signaling pathway, either by sequestering circulating ligands using decoy receptors (traps) or by blocking the intracellular tyrosine kinase domain of the fibroblast growth factor receptors (FGFRs) to prevent downstream signal transduction.