Denosumab: the era of targeted therapies in bone metastatic diseases.
This system constituted of the Receptor Activator of nuclear Factor-kB Ligand (RANKL), the Receptor Activator of Nuclear Factor-kB (RANK) and by the decoy Receptor Osteoprotegerin (OPG) plays a central role in bone resorption. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL.This review will critically describe and discuss the recent results of clinical trial investigating denosumab in different settings of medical oncology. In particular, we will report the recently published data of clinical trials investigating denosumab in prevention of cancer treatment induced bone loss (CTIBL), in prevention of skeletal related events (SREs) in bone metastatic patients and the ongoing studies in prevention of disease recurrence in the adjuvant setting of solid tumours. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of bone health care in cancer patients.
Santini
D
D
Medical Oncology, University Campus Bio-Medico, Rome, Italy.
Fratto
M E
ME
Vincenzi
B
B
Napoli
N
N
Galluzzo
S
S
Tantardini
M
M
Abbruzzese
A
A
Caraglia
M
M
Tonini
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary*; D016723:Bone Remodeling / Q000502:physiology; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D000069448:Denosumab; D016503:Drug Delivery Systems; D006801:Humans; D008954:Models, Biological; D053245:RANK Ligand / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000502:physiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000069448:Denosumab