Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Shu FengMichael Ittmann

Abstract

Extensive 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. Effects 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. AZ8010 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...Continue Reading

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Citations

Oct 12, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Longjiang ShaoMichael Ittmann
Jan 18, 2013·Biomolecular NMR Assignments·Navratna VajpaiAlexander L Breeze
Nov 23, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R DienstmannJ Tabernero
Jan 15, 2014·Cancer Metastasis Reviews·Rhonda L BittingAndrew J Armstrong
Feb 27, 2013·Cancer Research·Shu FengMichael Ittmann
Jul 24, 2015·Nature Communications·Tobias KleinAlexander L Breeze
Aug 26, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kaito YozaFuyuhiko Inagaki
Jan 1, 2013·Cancer Growth and Metastasis·Sathana DushyanthenGerald M Y Quan
May 31, 2019·Expert Opinion on Therapeutic Patents·Alvaro Quintanal-VillalongaLuis Paz-Ares
Sep 2, 2019·Cell and Tissue Research·Raquel Frenedoso da SilvaValéria Helena Alves Cagnon
Nov 30, 2018·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Gang XieLi-Li Zou
May 29, 2015·Oncotarget·Shu FengMichael Ittmann
Jun 30, 2019·Cell Biology and Toxicology·Clara H LeeRussell S Taichman
Sep 21, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paul G CornNora Navone
Oct 24, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Olga DakhovaMichael Ittmann
Aug 3, 2016·The Journal of Steroid Biochemistry and Molecular Biology·Senthilmurugan RamalingamVincent C O Njar
Mar 1, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R DienstmannJ Tabernero

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