Fibroblast growth factor in pancreatic development, homeostasis, and disease.

Abstract

Pancreatic development is a tightly orchestrated process driven by the concerted action of multiple signaling pathways. Fibroblast growth factors (FGFs) serve as pivotal cues across its stages: they engage FGF receptors (FGFRs) to activate downstream ERK/MAPK, PI3K-AKT, and PLCγ cascades, thereby governing pancreatic progenitor proliferation, differentiation, and functional maturation. The spatiotemporal expression of FGFs is precisely coupled to developmental milestones and intertwined with Notch, Wnt, and Hedgehog signaling in a complex regulatory network. This review systematically summarizes the molecular architecture and signal transduction of the FGF family, delineates its roles in pancreatic spatiotemporal dynamics, cell-fate determination, and maturation, examines how aberrant FGF signaling contributes to pancreatic cancer, diabetes, and pancreatitis, and reviews current FGF/FGFR-targeted therapies alongside their challenges. Future work must surmount technical bottlenecks and dissect cell-specific FGF mechanisms to underpin precision medicine for pancreatic disorders.