title: FGFR3 targeting strategies for achondroplasia.
abstract: Mutations that exaggerate signalling of the receptor tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) give rise to achondroplasia, the most common form of dwarfism in humans. Here we review the clinical features, genetic aspects and molecular pathogenesis of achondroplasia and examine several therapeutic strategies designed to target the mutant receptor or its signalling pathways, including the use of kinase inhibitors, blocking antibodies, physiologic antagonists, RNAi and chaperone inhibitors. We conclude by discussing the challenges of treating growth plate disorders in children.
authors.affiliation: Shriners Hospital for Children, Research Center, Portland, OR, USA.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: Laederich
authors.forename: William A
authors.initials: WA
authors.lastname: Horton
mesh_terms: D000130:Achondroplasia / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D000906:Antibodies; D047428:Protein Kinase Inhibitors; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3