title: The potential of fibroblast growth factor/fibroblast growth factor receptor signaling as a therapeutic target in tumor angiogenesis.
abstract: BACKGROUND
  Fibroblast growth factors (FGFs) are endowed with a potent pro-angiogenic activity. Activation of the FGF/FGF receptor (FGFR) system occurs in a variety of human tumors. This may lead to neovascularization, supporting tumor progression and metastatic dissemination. Thus, a compelling biologic rationale exists for the development of anti-FGF/FGFR agents for the inhibition of tumor angiogenesis in cancer therapy.
  
  
  METHODS
  A comprehensive search on PubMed was performed to identify studies on the role of the FGF/FGFR system in angiogenesis. Endothelial FGFR signaling, the pro-angiogenic function of canonical FGFs, and their role in human tumors are described. In addition, experimental approaches aimed at the identification and characterization of nonselective and selective FGF/FGFR inhibitors and their evaluation in clinical trials are summarized.
  
  
  CONCLUSIONS
  Different approaches can be envisaged to inhibit the FGF/FGFR system, a target for the development of 'two-compartment' anti-angiogenic/anti-tumor agents, including FGFR selective and nonselective small-molecule tyrosine kinase inhibitors, anti-FGFR antibodies, and FGF ligand traps. Further studies are required to define the correlation between tumor vascularization and activation of the FGF/FGFR system and for the identification of cancer patients more likely to benefit from anti-FGF/FGFR treatments. In addition, advantages and disadvantages about the use of selective versus non-selective FGF inhibitors remain to be elucidated.
authors.affiliation: a University of Brescia, Department of Molecular and Translational Medicine , Brescia, Italy +39 030 371 7311 ; marco.presta@unibs.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ronca
authors.affiliation: a University of Brescia, Department of Molecular and Translational Medicine , Brescia, Italy +39 030 371 7311 ; marco.presta@unibs.it.
authors.forename: Arianna
authors.initials: A
authors.lastname: Giacomini
authors.affiliation: a University of Brescia, Department of Molecular and Translational Medicine , Brescia, Italy +39 030 371 7311 ; marco.presta@unibs.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Rusnati
authors.affiliation: a University of Brescia, Department of Molecular and Translational Medicine , Brescia, Italy +39 030 371 7311 ; marco.presta@unibs.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Presta
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018450:Disease Progression; D015195:Drug Design; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors
keywords: angiogenesis; cancer; fibroblast growth factor; fibroblast growth factor receptor; therapeutic target