Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer

Abstract

Activation of the fibroblast growth factor receptor pathway is a common event in many cancer types. Here we review the role of fibroblast growth factor receptor signalling in breast cancer, from SNPs in FGFR2 that influence breast cancer risk and SNPs in FGFR4 that associate with breast cancer prognosis, and potential therapeutic targets such as receptor amplification and aberrant autocrine and paracrine ligand expression. We discuss the multiple therapeutic strategies in preclinical and clinical development and the current and future challenges to successfully targeting this pathway in cancer.

Figure 1

Alterations in the FGFR signalling pathway that influence breast cancer. Single nucleotide polymorphisms (SNPs) influence breast cancer risk (FGFR2), and prognosis in established cancers likely through effects on motility and invasive capacity (FGFR4). Somatic alterations presenting potential therapeutic targets include amplification of FGFR1 and FGFR2, and aberrant FGF2 ligand expressed in a paracrine or autocrine fashion.