Fibroblast growth factor 18 (FGF18) is a secreted signaling protein belonging to the FGF family, primarily involved in skeletal development, tissue repair, and cellular processes like proliferation and differentiation. It binds to FGFR3 and FGFR4 receptors, activating downstream pathways such as MAPK and PI3K/AKT. Dysregulation of FGF18 is linked to skeletal disorders, cancers, and fibrotic diseases.
FGF18 antibodies are therapeutic or research tools targeting either endogenous FGF18 (to block pathological signaling) or exogenous FGF18 (to enhance its regenerative effects). In oncology, neutralizing antibodies inhibit FGF18-driven tumor growth, angiogenesis, and metastasis, particularly in cancers with FGFR3/4 overexpression. Conversely, agonist antibodies or recombinant FGF18 administration has shown potential in bone/cartilage regeneration, notably in preclinical osteoarthritis models.
Clinical development includes antibodies like HLX22 (anti-FGF18) for gastric cancer and recombinant FGF18 (sprifermin) in Phase III trials for cartilage repair. Challenges include ensuring receptor specificity, minimizing off-target effects, and optimizing delivery for tissue-specific action. Future research focuses on antibody engineering for improved pharmacokinetics and combination therapies with biomaterials or gene editing tools.