Fibroblast growth factor receptor 1, 2, and 3 (IIIc isoforms) (FGFR1/2/3 IIIc)

Fibroblast growth factor receptors (FGFRs) 1, 2, and 3 are transmembrane receptor tyrosine kinases that regulate essential cellular processes including proliferation, differentiation, and angiogenesis (UniProt P11362, P21802, P22607). The IIIc isoforms are specific splice variants of the extracellular ligand-binding domain, typically associated with mesenchymal signaling and aggressive tumor phenotypes (PubMed: 11433380). In pancreatic cancer cell lines like COLO-357, the expression of FGFR1 IIIc, FGFR2 IIIc, and FGFR3 IIIc is linked to enhanced mitogenic signaling and resistance to apoptosis. These receptors are activated by various fibroblast growth factors (FGFs), leading to the activation of downstream pathways such as MAPK/ERK and PI3K/AKT. Pharmacological inhibition of these receptors using pan-FGFR inhibitors like erdafitinib or pemigatinib aims to disrupt these oncogenic signals. However, clinical use is often limited by off-target effects such as hyperphosphatemia and ocular toxicities.

Other names

FGFR1cFGFR2cFGFR3cCD331CD332CD333Mesenchymal fibroblast growth factor receptors

Competitive inhibition of the ATP-binding site within the intracellular tyrosine kinase domain of FGFR1, FGFR2, and FGFR3, preventing autophosphorylation and downstream signaling.