Careless talk costs lives: fibroblast growth factor receptor signalling and the consequences of pathway malfunction

Eight years ago, researchers Edward P. Carter, Abbie E. Fearon, and Richard P. Grose reviewed the role of fibroblast growth factor (FGF) receptor signalling in cellular behaviours and diseases. They found that FGF receptor signalling regulates development, homeostasis, and repair in various cell types, and dysfunctions in the FGF family can lead to developmental disorders and cancer. The deregulation can occur through receptor amplification, activating mutations, gene fusions, and receptor isoform switching. The researchers also discussed the potential therapeutic targeting of aberrant FGF signalling, noting that outcomes can be dependent on the activating ligand. They highlighted the role of FGFs in tissue repair and regeneration, particularly in the skin, liver, and lung, and their involvement in cancer. They found FGFR3 mutations in approximately 70% of non-muscle invasive bladder cancers and 45% of muscle invasive bladder cancers, and FGFR4 mutations in approximately 6% of rhabdomyosarcoma patients. The document also discussed the development of FGFR targeted therapies and the challenges in developing these therapeutic approaches.