Background:
Fibroblast growth factor (FGF) family is comprised of 23 highly regulated monomeric proteins which regulate a plethora of developmental and pathophysiological processes, including tissue repair, wound healing, angi-ogenesis, and embryonic development. Binding of FGF to fibroblast growth factor receptor (FGFR), a tyrosine kinase re-ceptor, is facilitated by a glycosaminoglycan, heparin. Activated FGFRs phosphorylate the tyrosine kinase residues that mediate induction of downstream signaling pathways such as RAS-MAPK, PI3K-AKT, PLCγ, and STAT. Dysregulation of the FGF/FGFR signaling occurs frequently in cancer due to gene amplification, FGF activating mutations, chromosomal rearrangements, integration, and oncogenic fusions. Aberrant FGFR signaling also affects the organogenesis, embryonic development, tissue homeostasis, and has been associated with cell proliferation, angiogenesis, cancer, and other patho-physiological changes.
Objective:
This comprehensive review will discuss the biology, chemistry and functions of FGFs, and its current applica-tions toward wound healing, diabetes, repair and regeneration of tissues, and fatty liver diseases. In addition, specific aber-rations in FGFR signaling, and drugs that target FGFR and aid in mitigating various disorders, such as cancer are also discussed in detail.
Conclusion:
Inhibitors of FGFR signaling are promising drugs in the treatment of several types of cancers. The clinical benefits of FGF/FGFR targeting therapies is impeded due to activation of other RTK signaling mechanisms or due to the mutations that abolish the drug inhibitory activity on FGFR. Thus, development of drugs with different mechanism of action for FGF/FGFR targeting therapies is the recent focus of several preclinical and clinical studies.