title: Molecular target therapy for bone metastasis: starting a new era with denosumab, a RANKL inhibitor.
abstract: BACKGROUND
  The skeleton is generally the primary, and sometimes the only, site of metastasis in patients with advanced solid tumors. Bone metastases are the most frequent cause of cancer-related pain and the origin of severe morbidity in patients. Among the treatment options available for the prevention of skeletal-related events (SREs) associated with bone metastasis, zoledronic acid, an antiresorptive treatment from the group of bisphosphonates, is currently the standard of care in this setting.
  
  
  METHODS
  Zoledronic acid, together with denosumab (a monoclonal antibody against the receptor activator of nuclear factor kappa B ligand), is the most frequent approach for the prevention of cancer-related events in skeleton. This paper reviews several trials evaluating the efficacy of denosumab in comparison with zoledronic acid in patients with solid osteotropic tumors. In this setting of skeleton-invading cancers, denosumab was demonstrated to be superior to zoledronic acid in preventing or delaying SREs. In comparison with zoledronic acid, denosumab significantly delayed the time to first SRE by 17%.
  
  
  CONCLUSIONS
  Current research on denosumab is addressed to prove the immunomodulator effect of this agent in humans. Other avenue of research is focused on its antitumor activity observed in some Phase III trials.
authors.affiliation: Professor, Head of Phase I-Early Clinical Trials Unit, Antwerp University Hospital UZA, Oncology Department , Wilrijkstraat 10, 2650 Edegem , Belgium +32 3 821 36 46 ; christian.rolfo@uza.be.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Noemí
authors.initials: N
authors.lastname: Reguart
authors.forename: Rosario García
authors.initials: RG
authors.lastname: Campelo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bronte
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Papadimitriou
authors.forename: Franco
authors.initials: F
authors.lastname: Silvestris
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D058990:Molecular Targeted Therapy; D017410:Practice Guidelines as Topic; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab; D000077211:Zoledronic Acid