title: Denosumab: benefits of RANK ligand inhibition in cancer patients.
abstract: OBJECTIVE
  RANK ligand (RANKL) plays a central role in the cancer-induced bone destruction that results from bone metastasis. The RANKL inhibitor denosumab was recently approved for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. This review summarizes recent findings of the effects of RANKL inhibition and denosumab in the cancer setting.
  
  
  RESULTS
  Preclinical data show that RANKL inhibition in combination with antitumor therapies has additive effects on preventing skeletal tumor progression. Preclinical breast cancer models also suggest RANKL may be involved in primary tumorigenesis and establishment of metastases in bone and other tissues. Pivotal clinical trial data with denosumab in advanced cancer patients across tumor types showed it was superior (breast and prostate) or noninferior trending toward superior (solid tumors/multiple myeloma) to zoledronic acid, in reducing the risk of developing an SRE and demonstrated a favorable safety profile. Denosumab has also demonstrated efficacy in the treatment of giant cell tumor of bone.
  
  
  CONCLUSIONS
  Denosumab offers an important new treatment option for patients with solid tumors and bone metastases. The efficacy of RANKL inhibition with denosumab in other disease states in the cancer setting continues to be evaluated.
authors.affiliation: Penn State Hershey Medical Center, Hershey, Pennsylvania, USA. alipton@psu.edu
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobs
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000188:drug therapy; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000077211:Zoledronic Acid
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053245:RANK Ligand; D000069448:Denosumab; D000077211:Zoledronic Acid