FGF19 promotes progression of prostate cancer

  title={FGF19 promotes progression of prostate cancer},
  author={Hirotaka Nagamatsu and Jun Teishima and Keisuke Goto and Hiroyuki Shikuma and Hiroyuki Kitano and Koichi Shoji and Shogo Inoue and Akio Matsubara},
  journal={The Prostate},
Fibroblast growth factor (FGF) signaling pathways have been reported to play important roles in prostate cancer (PCa) progression. FGF19 is one of a subfamily of FGFs that circulate in serum and act in an endocrine manner. Our objective was to investigate its role in the progression of PCa. 
Making way for suppressing the FGF19/FGFR4 axis in cancer.
Considering the critical role of this receptor complex in cancer, this review focuses on recent developments and applications of FGF19/FGFR4-targeted therapeutics.
Upregulation of FGF 19 in lung adenocarcinoma and predicts poor prognosis
Analysis of the expression of FGF19 in LAC tissues and corresponding normal tissues suggested that up-regulation of F GF19 might potentially be an effective therapeutic approach for LAC.
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The increasing understanding of the differences between diverse mechanisms of oncogenic activation of FGFR, and the factors that determine response and resistance to FGFR targeting are discussed.
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Targeting the fibroblast growth factor receptor family in cancer.
Upregulation of Fibroblast Growth Factor 19 Is Associated with the Initiation of Colorectal Adenoma
Observations indicate that the FGF19/FGFR4 pathway may be involved in the development of neoplasia, and that FGF 19 may be a valuable diagnostic marker for the identification of patients with colorectal adenomas.
The potential of fibroblast growth factor/fibroblast growth factor receptor signaling as a therapeutic target in tumor angiogenesis
A compelling biologic rationale exists for the development of anti-FGF/FGFR agents for the inhibition of tumor angiogenesis in cancer therapy, including FGFR selective and nonselective small-molecule tyrosine kinase inhibitors, anti-FGFR antibodies, and FGF ligand traps.
FGF21 facilitates autophagy in prostate cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway
The findings show that FGF21 inhibits PCa cell proliferation and promoted apoptosis in PCa cells through facilitated autophagy, which might be a potential novel target in PCA therapy.
Future applications of FGF/FGFR inhibitors in cancer
It appears mandatory to identify FGF/FGFR alterations and appropriate biomarkers that may predict and monitor response to treatment, to establish the contribution of the FGF-FGFR system to the onset of mechanisms of drug resistance, and to develop effective combinations of FGF /FGFR inhibitors with other targeted therapies.
Enhanced autocrine FGF19/FGFR4 signaling drives the progression of lung squamous cell carcinoma, which responds to mTOR inhibitor AZD2104
It is reported for the first time that inhibiting mTOR pathway by using AZD2014 was effective and feasible and offered a new strategy by using anti-FGF19/FGFR4 therapy or mTOR-based therapy in FGF19-driven LSQ.


Endocrine fibroblast growth factor FGF19 promotes prostate cancer progression.
It is shown that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor, supporting the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlighting FGF 19 as a relevant endocrine FGF in this setting.
Alterations in expression of basic fibroblast growth factor (FGF) 2 and its receptor FGFR-1 in human prostate cancer.
  • D. GiriF. RopiquetM. Ittmann
  • Biology, Medicine
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1999
There is both an increase in FGF2 concentration in prostate cancers and an increased expression of a receptor capable of responding to this growth factor, establishing a potential paracrine stimulation of prostate cancer cells by the surrounding stromal cells, which may play an important role in prostate cancer progression.
Evidence for distinct alterations in the FGF axis in prostate cancer progression to an aggressive clinical phenotype
It is demonstrated that increased FGFR4 and reduced Sef may be critical FGF alterations associated with prostate cancer progression and may also have a role in the tumour response to FGFR inhibition and warrants further investigation.
Evaluation of the fibroblast growth factor system as a potential target for therapy in human prostate cancer
The model of FGF system as valid target for therapy in CaP is supported and synergistic effects on in vitro cell growth (proliferation and colony formation) by combining sFGFR expression and treatment with either Paclitaxel (Taxol®) or γ-irradiation are confirmed.
Inhibition of fibroblast growth factor 19 reduces tumor growth by modulating beta-catenin signaling.
FGF19/FGFR4 cross-talk with beta-catenin and that pathway intervention reduces tumor growth is highlighted and wild-type beta-Catenin is accessible for modulation.
The Klotho gene family as a regulator of endocrine fibroblast growth factors
Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models
It is reported that fibroblast growth factor 19 and its cognate receptor FGF receptor 4 are coexpressed in primary human liver, lung and colon tumors and in a subset of human colon cancer cell lines, and an anti-FGF19 monoclonal antibody is developed that selectively blocks the interaction of FGF19 with FGFR4.
Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.
It is reported that FGF19 transgenic mice had a significant and specific reduction in fat mass that resulted from an increase in energy expenditure and did not become obese or diabetic on a high fat diet.
FGF-21 as a novel metabolic regulator.
It is concluded that FGF-21, which was discovered to be a potent regulator of glucose uptake in mouse 3T3-L1 and primary human adipocytes, exhibits the therapeutic characteristics necessary for an effective treatment of diabetes.
Fibroblast growth factor 19 serum levels: relation to renal function and metabolic parameters.
It is demonstrated that circulating FGF19 levels are significantly increased in end-stage renal disease and FGF 19 is associated with a beneficial metabolic profile in both control and CD patients.