FGFR signalling in women's cancers

Abstract

FGFs, in a complex with their receptors (FGFRs) and heparan sulfate (HS), are responsible for a range of cellular functions, from embryogenesis to metabolism. Both germ line and somatic FGFR mutations are known to play a role in a range of diseases, most notably craniosynestosis dysplasias, dwarfism and cancer. Because of the ability of FGFR signalling to induce cell proliferation, migration and survival, FGFRs are readily co-opted by cancer cells. Mutations in, and amplifications of, these receptors are found in a range of cancers with some of the most striking clinical findings relating to their contribution to pathogenesis and progression of female cancers. Here, we outline the molecular mechanisms of FGFR signalling and discuss the role of this pathway in women's cancers, focusing on breast, endometrial, ovarian and cervical carcinomas, and their associated preclinical and clinical data. We also address the rationale for therapeutic intervention and the need for FGFR-targeted therapy to selectively target cancer cells in view of the fundamental roles of FGF signalling in normal physiology.

Keywords: AuNP; CCC; CIN; CISH; CLC; Cancer; DCIS; EEC; ER; FGF; FGFR; FISH; Fibroblast growth factor (FGF); Fibroblast growth factor receptor (FGFR); GWAS; Genome Wide Association Study; HPV; HS; IDC; IHC; MSI; NEEC; PDGFR; PR; RTK; SC; SNP; Saethre Chotzen; Signalling; TIC; TKI; TMA; Therapy; VEGFR; cervical intraepithelial neoplasia; chromogenic in situ hybridisation; classic lobular carcinoma; clear cell carcinoma; ductal carcinoma in situ; endometrioid endometrial carcinoma; fibroblast growth factor; fibroblast growth factor receptor; fluorescence in situ hybridisation; gold nanoparticle; heparan sulfate; human papilloma virus; immunohistochemistry; invasive ductal carcinoma; mAb; microsatellite instability; monoclonal antibody; non-endometrioid endometrial carcinoma; oestrogen receptor; platelet-derived growth factor receptor; progesterone receptor; receptor tyrosine kinase; small nucleotides polymorphism; tissue microarray; tumour initiating cell; tyrosine kinase inhibitor; vascular endothelial growth factor receptor.