Abstract
Fibroblast growth factor receptor 4 (FGFR4) is a tyrosine kinase receptor that is a member of the fibroblast growth factor receptor family and is stimulated by highly regulated ligand binding. Excessive expression of the receptor and its ligand, especially FGF19, occurs in many types of cancer. Abnormal FGFR4 production explains these cancer formations, and therefore, this receptor has emerged as a potential target for inhibiting cancer development. This review discusses the diverse mechanisms of oncogenic activation of FGFR4 and highlights some currently available inhibitors targeting FGFR4.
Highlights
FGFR1–4 and FGFR5 comprise the fibroblast growth factor receptor (FGFR) family (Wang and Ding, 2017)
Improving our understanding of the pathogenesis that occurs in tumors that overexpress Fibroblast growth factor receptor 4 (FGFR4), as well as the elucidation of elements that alter the sensitivity to endurance of FGFR4 inhibitors, is vital for a more accurate selection of patients and for increasing the success rate of cancer treatment with FGFR4 inhibitors (Knights and Cook, 2010)
Many investigations and studies have demonstrated that the FGF19/FGFR4 pathway influences cells’ growth, development, and their differentiation in tumors (Katoh, 2016)
Summary
FGFR1–4 and FGFR5 comprise the fibroblast growth factor receptor (FGFR) family (Wang and Ding, 2017). The result suggests that inflammatory cytokines, especially IL-1β, can influence the activation of the FGF19/ FGFR4 signaling pathway in the tumor microenvironment. A recent study found that breast cancer cell lines can express FGFR4 to gain the ability to resist apoptosis when treated with cyclophosphamide and doxorubicin, while this capacity disappears when the FGFR4 gene is silenced (Andre and Cortes, 2015). Another study showed that drug-resistant cells activate FGFR4 signaling to phosphorylate FGF receptor substrate 2 (FRS2) and activate downstream MAPK/ERK signaling. One recent study revealed that SNHG16 increased HCC growth and antiapoptosis through the SNHG16/miR-302a-3p/FGF19 pathway (Li et al, 2019) These studies indicate that FGF19 is associated with tumorigenesis, and targeting it may be useful as a form of cancer therapy. Recurrent resectable unresectable glioblastoma Oncogenic osteomalacia Non–small-cell lung cancer Breast cancer Carcinoma, hepatocellular Urothelial cancer
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