Fibroblast Growth Factor Signalling: From Development to Cancer

Nicholas Turner; Richard Grose

In This Article

Abstract and Introduction


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.


Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate fundamental developmental pathways, controlling events such as mesoderm patterning in the early embryo[1] through to the development of multiple organ systems.[2] FGF signalling extends to many physiological roles in the adult organism, including the regulation of angiogenesis and wound repair. FGFRs are expressed on many different cell types and regulate key cell behaviours, such as proliferation, differentiation and survival, which makes FGF signalling susceptible to subversion by cancer cells.

There is compelling evidence for deregulated FGF signalling in the pathogenesis of many cancers that originate from different tissue types. Aberrant FGF signalling can promote tumour development by directly driving cancer cell proliferation and survival, and by supporting tumour angiogenesis. Mouse models have confirmed that FGF signalling has oncogenic potential, but have also importantly demonstrated that FGF signalling can have tumour suppressive functions in certain contexts. Coupled with the importance of FGF signalling in tissue development and homeostasis, this underlines the importance of appropriate targeting of any potential therapeutic interventions.


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