Advances and challenges in targeting FGFR signalling in cancer

Deregulation of fibroblast growth factor (FGF) signalling is observed in several types of cancer, which makes this pathway a highly promising potential therapeutic target. However, aberrant FGF receptor (FGFR) signalling can be challenging. In this Review, Babinaet al. discuss the differences between diverse mechanisms of oncogenic activation of FGFR, and the factors that determine response and resistance to FGFR targeting. Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate numerous cellular processes. Deregulation of FGFR signalling is observed in a subset of many cancers, making activated FGFRs a highly promising potential therapeutic target supported by multiple preclinical studies. However, early-phase clinical trials have produced mixed results with FGFR-targeted cancer therapies, revealing substantial complexity to targeting aberrant FGFR signalling. In this Review, we discuss the increasing understanding of the differences between diverse mechanisms of oncogenic activation of FGFR, and the factors that determine response and resistance to FGFR targeting.