Fibroblast growth factor receptor 2 IIIb isoform (FGFR2IIIb)

Fibroblast growth factor receptor 2 IIIb isoform (FGFR2IIIb), also known as keratinocyte growth factor receptor (KGFR), is a transmembrane tyrosine kinase receptor produced through alternative splicing of the FGFR2 gene (NIH, 2026; UniProt, 2024). It is predominantly expressed in epithelial tissues and selectively binds ligands such as FGF7 (KGF), FGF10, and FGF22, which are typically produced by neighboring mesenchymal cells (NIH, 2004; OncLive, 2025). This paracrine signaling pathway is essential for normal embryonic development, particularly in the morphogenesis of the lungs, limbs, and skin, as well as for adult tissue repair and homeostasis (NIH, 2000; UniProt, 2024). In oncology, FGFR2IIIb is a significant therapeutic target due to its frequent overexpression or gene amplification in various solid tumors, most notably gastric and gastroesophageal junction adenocarcinomas (OncLive, 2025; MDPI, 2022). Aberrant signaling through this receptor promotes tumor cell proliferation, survival, and angiogenesis, often correlating with poor prognosis (NIH, 2026; MDPI, 2022). Therapeutic interventions include monoclonal antibodies like bemarituzumab, which inhibits ligand binding and induces antibody-dependent cell-mediated cytotoxicity (ADCC) (OncLive, 2025). Additionally, small-molecule tyrosine kinase inhibitors are used to block the receptor's intracellular signaling, although they often target multiple FGFR isoforms (MDPI, 2022). Clinical management of patients targeting this receptor requires monitoring for specific toxicities, such as corneal events and stomatitis (OncLive, 2025).

Other names

Keratinocyte growth factor receptorKGFRFGFR2bFibroblast growth factor receptor 2 isoform IIIbCD332BEKBacteria-expressed kinase

Monoclonal antibody-mediated inhibition of ligand binding and induction of antibody-dependent cell-mediated cytotoxicity (ADCC), and small-molecule inhibition of receptor tyrosine kinase autophosphorylation and downstream signaling pathways (e.g., MAPK, PI3K/AKT).