A patent review of FGFR4 selective inhibition in cancer (2007-2018).

INTRODUCTION: FGFR4 is a tyrosine kinase receptor which, under physiological conditions, is activated upon ligand binding in a highly regulated manner. This triggers downstream signaling related to proliferation and apoptosis resistance as well as other physiological processes. Many molecular alterations of the receptor and its ligands, specially FGF19, have been reported in several types of cancer, with special relevance in hepatocellular carcinoma. In addition, these have also been detected in other solid malignancies, including lung, breast, or colon cancer, among others. AREAS COVERED: This review covers patent literature on specific FGFR4 inhibitors and their applications, published from 2007 to June 2018. EXPERT OPINION: FGFR4 inhibition has gained relevance in oncology. A considerable number of patents disclosing different approaches to inhibit this receptor have been reported, displaying promising preclinical results for different cancer models. Currently, the safety and preliminary efficacy of several small molecule inhibitors targeting FGFR4 are under early phase clinical assessment, mainly in hepatocellular carcinoma patients. If positive results are derived from these trials, they will open the door for the application of FGFR4 small molecule inhibitors to a wide population of tumors of different types that harbor FGFR4-FGF19 signaling dysregulation.