title: The role of RANK-ligand inhibition in cancer: the story of denosumab.
abstract: The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular.
authors.affiliation: Medical Oncology Service, Hospital Universitario 12 de Octubre, Avda. De Córdoba, 28041 Madrid, Spain. cdanicas@hotmail.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Sepulveda
authors.forename: Ignacio
authors.initials: I
authors.lastname: García-Escobar
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rodriguez-Antolín
authors.forename: Anna
authors.initials: A
authors.lastname: Sundlöv
authors.forename: Hernán
authors.initials: H
authors.lastname: Cortes-Funes
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D016723:Bone Remodeling / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D002986:Clinical Trials as Topic; D000069448:Denosumab; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000627:therapeutic use; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000069448:Denosumab