Fibroblast growth factor receptor 2 (FGFR2) IIIc isoform (FGFR2c)

The Fibroblast growth factor receptor 2 (FGFR2) IIIc isoform is a mesenchymal splice variant of the FGFR2 protein, characterized by the inclusion of exon 9 in the third immunoglobulin-like domain of its extracellular region [NIH, 2021]. Under normal physiological conditions, this isoform is primarily expressed in mesenchymal tissues and mediates paracrine signaling by binding to ligands such as FGF2, FGF4, and FGF6 [AACR, 2012]. In the context of oncology, a pathological 'isoform switch' from the epithelial IIIb variant to the mesenchymal IIIc variant is a hallmark of the epithelial-mesenchymal transition (EMT) [ResearchGate, 2021]. This transition enhances the invasive and metastatic potential of tumor cells and is frequently observed in cancers of the stomach, colon, and prostate [NIH, 2025]. High expression of the FGFR2 IIIc isoform is a significant prognostic biomarker for poor survival and has been implicated as a mechanism of resistance to therapies targeting the IIIb isoform [ESMO Open, 2025]. Current therapeutic strategies involve pan-FGFR tyrosine kinase inhibitors that target the conserved intracellular kinase domain, while research into isoform-specific monoclonal antibodies aims to provide more selective targeting of the IIIc variant [AACR, 2012].

Other names

FGFR2-IIIcFGFR2cMesenchymal FGFR2FGFR2 exon 9 variantFibroblast growth factor receptor 2c

Inhibition of the intracellular tyrosine kinase domain, blocking downstream signaling pathways such as MAPK/ERK and PI3K/AKT [Insilico Medicine, 2024]; competitive inhibition of ATP binding; and potential ligand-blocking by isoform-specific antibodies [AACR, 2012].