Inhibition of FGFR4: Adding to the Arsenal of Anti-FGFR Agents

Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia. Corresponding Author: Pamela M. Pollock, Institute of Health and Biomedical Innovation, 37 Kent Street, Woolloongabba, Brisbane, QLD 4102, Australia. Phone: 61-7-3443-7237; Fax: 61-7-3443-7779; E-mail: pamela. [email protected] doi: 10.1158/2159-8290.CD-15-0246 ©2015 American Association for Cancer Research. Summary: In this issue of Cancer Discovery , Hagel and colleagues report the design and the in vitro and in vivo activity of a novel, irreversible, paralog-specifi c kinase inhibitor of FGFR4, BLU9931. This compound binds covalently to a cysteine residue in the hinge region of FGFR4 but not in FGFR1–3. BLU9931 induces tumor shrinkage in hepatocellular carcinoma models that express a functioning ligand/receptor complex consisting of FGF19/ FGFR4/KLB and adds to a growing list of anti-FGFR4 agents. Cancer Discov; 5(4); 355–7. ©2015 AACR .