Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine
and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger
a variety of cellular processes including angiogenesis, evasion from apoptosis, bone formation,
embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation,
cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore,
gain-of-function or loss-of-function in FGFRs1-4 which is due to amplification, fusions, mutations,
and changes in tumor–stromal cells interactions, is associated with the development and progression
of cancer. Although, the developed small molecule or antibodies targeting FGFR signaling offer immense
potential for cancer therapy, emergence of drug resistance, activation of compensatory pathways
and systemic toxicity of modulators are bottlenecks in clinical application of anti-FGFRs. In this
review, we present FGF/FGFR structure and the mechanisms of its function, as well as cross-talks
with other nodes and/or signaling pathways. We describe deregulation of FGF/FGFR-related mechanisms
in human disease and tumor progression leading to the presentation of emerging therapeutic approaches,
resistance to FGFR targeting, and clinical potentials of individual FGF family in several
human cancers. Additionally, the underlying biological mechanisms of FGF/FGFR signaling, besides
several attempts to develop predictive biomarkers and combination therapies for different cancers
have been explored.
Focal Contact and Hemidesmosomal Proteins in Keratinocyte Migration and Wound Repair
