Journal Article

Fibroblast growth factor signalling: from development to cancer

Grose, Richard, Turner, Nicholas

2010

Overview

Key Points Fibroblast growth factors (FGFs) and their receptors (FGFRs) drive crucial developmental signalling pathways, which are responsible for many functions, including cell proliferation, survival and migration. As such, they are susceptible to hijack by cancer cells and have been shown to have oncogenic roles in many cancers. Conversely, FGFR signalling can also have tumour suppressive roles, through driving differentiation, regulating other oncogenic pathways, protecting cells from damage or perhaps by mediating immune surveillance. The specific cellular context in which FGF signalling occurs is clearly important for determining whether oncogenic or tumour protective outcomes are evoked, and understanding more about context-specific FGF signalling is a key area of research. There are several types of genetic evidence that support an oncogenic function for FGFRs: identification of gene amplifications, activating mutations, chromosomal translocations, single nucleotide polymorphisms and aberrant splicing at the post-transcriptional level. Expression of FGFs can also be affected by gene amplification. There is now evidence from multiple cancer types to implicate FGF signalling in several oncogenic behaviours, including proliferation, survival, migration, invasion and angiogenesis. Therapeutic targeting of FGFs and their receptors is a major area of drug development research. Most agents are small-molecule tyrosine kinase inhibitors, but blocking antibodies and ligand-trap approaches are also being developed. Fibroblast growth factors (FGFs) and their receptors have been shown to drive tumorigenesis and tumour progression. However, FGF signalling can also be tumour suppressive, and understanding the mechanisms that underlie these context-specific effects will be important to rationally target FGF signalling for therapeutic benefit. Fibroblast growth factors (FGFs) and their receptors control a wide range of biological functions, regulating cellular proliferation, survival, migration and differentiation. Although targeting FGF signalling as a cancer therapeutic target has lagged behind that of other receptor tyrosine kinases, there is now substantial evidence for the importance of FGF signalling in the pathogenesis of diverse tumour types, and clinical reagents that specifically target the FGFs or FGF receptors are being developed. Although FGF signalling can drive tumorigenesis, in different contexts FGF signalling can mediate tumour protective functions; the identification of the mechanisms that underlie these differential effects will be important to understand how FGF signalling can be most appropriately therapeutically targeted.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/67 / 631/80/86 / 692/420/755 / Angiogenesis / Biomedicine / Blocking antibodies / Cancer / Cancer Research / Cell migration / Cell Proliferation / Cell survival / Cellular signal transduction / Chromosome translocations / Drug development / Fibroblast growth factor receptors / Fibroblast growth factors / Fibroblast Growth Factors - antagonists & inhibitors / Fibroblast Growth Factors - genetics / Fibroblast Growth Factors - metabolism / Fibroblasts / Gene Amplification / Gene mutations / Growth factors / Health aspects / Humans / Immunosurveillance / Kinases / Neoplasm Invasiveness / Neoplasms - genetics / Neoplasms - metabolism / Phosphorylation / Physiological aspects / Post-transcription / Protein-tyrosine kinase / Receptors, Fibroblast Growth Factor - antagonists & inhibitors / Receptors, Fibroblast Growth Factor - genetics / Receptors, Fibroblast Growth Factor - metabolism / review-article / Signal Transduction / Single-nucleotide polymorphism / Therapeutic targets / Translocation, Genetic / Tumorigenesis / Tumors / Tyrosine