title: [Treatment of bone metastasis by denosumab, the human monoclonal neutralizing antibody to RANKL].
abstract: Solid cancers such as breast, prostate and lung cancer have a predilection for spreading to bone. Accumulating data suggest that the crosstalk between metastatic cancer cells and bone-resorbing osteoclasts plays a central role in the development and progression of bone metastases. Recent studies have revealed that osteoblasts mediate this crosstalk by expressing the receptor activator of NF-kappaB ligand (RANKL) in response to cancer-produced osteotropic factors. The RANKL promotes osteoclast formation and bone resorption via the binding to RANK expressed in hematopoietic osteoclast precursor cells and mature osteoclasts. Denosumab is the humanized anti-RANKL neutralizing monoclonal antibody and thus would be a specific and effective therapeutic agent for the treatment of bone metastases. In fact, clinical studies clearly demonstrated that denosumab significantly inhibited the development of skeletal-related events associated with bone metastases and indicate its usefulness for bone metastases.
authors.affiliation: Division of Hematology/Oncology, Indiana University School of Medicine.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
mesh_terms: D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects* / Q000276:immunology; D053245:RANK Ligand / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D053245:RANK Ligand