Clinical development of anti-RANKL therapies for treatment and prevention of bone metastasis

Bone. 2011 Jan;48(1):96-9. doi: 10.1016/j.bone.2010.10.161. Epub 2010 Oct 13.

Abstract

The clinical sequelae from bone metastases, termed skeletal-related events, are among the most frequent and debilitating complications in patients with advanced cancer. Bone metastases are characterized by pathologically increased osteoclast activity, and accumulating evidence indicates that tumor cells interact within the bone to stimulate the RANK-RANK ligand (RANKL) pathway. RANKL is an essential mediator of osteoclast formation, function, and survival. Because of the central role of RANKL in cancer-induced bone destruction, the inhibition of RANKL has the potential to result in the reduction of pathologic bone resorption. Denosumab is a fully human monoclonal antibody specific for RANKL that inhibits the formation, activation, and survival of osteoclasts. This in turn decreases bone resorption and reduces cancer-induced bone destruction. As a result of its unique and specific mechanism of action, denosumab is being investigated for use in patients with advanced malignancies involving bone to prevent the occurrence of skeletal-related events.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Bone Marrow Neoplasms* / drug therapy
  • Bone Marrow Neoplasms* / metabolism
  • Bone Marrow Neoplasms* / prevention & control
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / prevention & control
  • Bone Neoplasms* / secondary
  • Bone Resorption / metabolism
  • Bone Resorption / physiopathology
  • Bone Resorption / prevention & control
  • Bone and Bones / metabolism
  • Bone and Bones / physiopathology
  • Clinical Trials as Topic
  • Denosumab
  • Humans
  • Osteoclasts / metabolism
  • RANK Ligand / antagonists & inhibitors*
  • RANK Ligand / immunology
  • RANK Ligand / metabolism*
  • RANK Ligand / pharmacology
  • RANK Ligand / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • RANK Ligand
  • Denosumab