FGFBPs in health and tumors: emerging prognostic biomarkers and therapeutic implications

The fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway is essential for maintaining physiological homeostasis, and its dysregulation is implicated in the pathogenesis of numerous diseases. FGF-binding proteins (FGFBPs) constitute a family of secreted proteins that modulate the bioavailability of FGF ligands, thereby fine-tuning FGF signaling output in a context-specific manner. Emerging evidence indicates that FGFBPs regulate diverse physiological processes, including embryonic development, tissue repair, and metabolic homeostasis, while dysregulation of these members is closely associated with various diseases, particularly malignancies. Nevertheless, their precise functional roles in physiological homeostasis and oncogenesis, as well as the underlying molecular mechanisms governing these functions, remain incompletely characterized. This review systematically summarizes the physiological functions of FGFBPs, with a focused analysis of their context-dependent roles in diverse types of cancer. We further discuss their emerging potential as prognostic biomarkers and therapeutic implications. A deeper mechanistic understanding of FGFBPs is expected to advance insights into the molecular underpinnings of both physiological homeostasis and tumorigenesis, thereby informing the rational development of novel diagnostic biomarkers and precise therapeutic intervention strategies.