title: Giant cell tumor of bone in childhood: clinical aspects and novel therapeutic targets.
abstract: Giant cell tumor of bone (GCTB) is a rare primary bone tumor that primarily affects young adults, but can be seen in children. The primary modality of treatment is surgical resection; however, this is not always possible given the location and extent of the neoplasm. Recent developments in the understanding of the underlying molecular pathogenesis of disease have pointed to interactions between the stromal component producing receptor activator of nuclear factor-kappaB (RANK) and RANK-ligand (RANKL) causing the formation of osteoclast-like giant cells that drive bone destruction. The development of a monoclonal humanized antibody to RANKL, denosumab, has been shown to reduce skeletal-related events from osteoporosis and from bony metastases from solid tumors. Recent phase II clinical trials with denosumab in skeletally mature adolescents over age 12 years and adults with GCTB, have shown both safety and efficacy, leading to its accelerated US FDA approval on 13 June 2013. In children who are skeletally immature, safety and efficacy has not been established, and there has been only published anecdotal use.
authors.affiliation: Department of Pediatrics, Hematology/Oncology, Mattel Children's Hospital at University of California, Los Angeles, USA, nfederman@mednet.ucla.edu.
authors.forename: Noah
authors.initials: N
authors.lastname: Federman
authors.forename: Earl W
authors.initials: EW
authors.lastname: Brien
authors.forename: Vivek
authors.initials: V
authors.lastname: Narasimhan
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Dry
authors.forename: Monish
authors.initials: M
authors.lastname: Sodhi
authors.forename: Sant P
authors.initials: SP
authors.lastname: Chawla
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D000069448:Denosumab; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000069448:Denosumab