ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Characterization of FGFR signaling in prostate cancer stem cells and inhibition via TKI treatment.Oncotarget · 2021Article
- Therapeutic implications of fibroblast growth factor receptor inhibitors in a combination regimen for solid tumors.Oncology letters · 2020Review
- Bone microenvironment signaling of cancer stem cells as a therapeutic target in metastatic prostate cancer.Cell biology and toxicology · 2020Review
- FGFR1 and FGFR4 oncogenicity depends on n-cadherin and their co-expression may predict FGFR-targeted therapy efficacy.EBioMedicine · 2020Article
- Article
- Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer.Frontiers in cell and developmental biology · 2020Review
- Offsetting Expression Profiles of Prognostic Markers in Prostate Tumor vs. Its Microenvironment.Frontiers in oncology · 2019Article
- FGFR1 is an independent prognostic factor and can be regulated by miR-497 in gastric cancer progression.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018Article
- Fibroblast growth factor receptor signaling plays a key role in transformation induced by the TMPRSS2/ERG fusion gene and decreased PTEN.Oncotarget · 2018Article
- Dissecting major signaling pathways in prostate cancer development and progression: Mechanisms and novel therapeutic targets.The Journal of steroid biochemistry and molecular biology · 2017Review
- Combination treatment of prostate cancer with FGF receptor and AKT kinase inhibitors.Oncotarget · 2017Article
- Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network.Oncotarget · 2015Article
- In vitro and in vivo evaluation of the radiosensitizing effect of a selective FGFR inhibitor (JNJ-42756493) for rectal cancer.BMC cancer · 2015Article
- Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase.Nature communications · 2015Article
- FGF23 promotes prostate cancer progression.Oncotarget · 2015Article
- Article
- Secretome analysis of an osteogenic prostate tumor identifies complex signaling networks mediating cross-talk of cancer and stromal cells within the tumor microenvironment.Molecular & cellular proteomics : MCP · 2015Article
- Dovitinib (TKI258), a multi-target angiokinase inhibitor, is effective regardless of KRAS or BRAF mutation status in colorectal cancer.American journal of cancer research · 2015Article
- The role of epithelial plasticity in prostate cancer dissemination and treatment resistance.Cancer metastasis reviews · 2014Review
- Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors.Annals of oncology : official journal of the European Society for Medical Oncology · 2014Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
purposeExtensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. EXPERIMENTAL
designEffects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model.
resultsAZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors.
conclusionsTargeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.
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