The potential of fibroblast growth factor/fibroblast growth factor receptor signaling as a therapeutic target in tumor angiogenesis

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• angiogenesis
• cancer
• fibroblast growth factor
• fibroblast growth factor receptor
• therapeutic target

Declaration of interests

This work was supported in part by grants from Ministero dell’Istruzione, Università e Ricerca (FIRB project RBAP11H2R9 2011), and Associazione Italiana per la Ricerca sul Cancro (AIRC grant n° 14395) to M Presta. A Giacomini was supported by a Fondazione Italiana per la Ricerca sul Cancro Fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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