RANKL inhibition: clinical implications for the management of patients with multiple myeloma and solid tumors with bone metastases.
BACKGROUND
Receptor activator of NF-kappaB ligand (RANKL) binds to RANK on the surface of osteoclast precursors and enhances their differentiation, survival and fusion, activates mature osteoclasts and inhibits their apoptosis. Osteoprotegerin (OPG) is the decoy receptor of RANKL. Disruption of the RANK/RANKL/OPG axis is implicated in bone metastases.


OBJECTIVE
A review of the role of RANKL signaling in bone development and the rationale for targeting RANKL in treatment of bone metastases and myeloma bone disease.


CONCLUSIONS
In preclinical models of solid tumors and myeloma, RANKL inhibition reduced osteoclast numbers and subsequent bone resorption, prevented development of osteolytic lesions and decreased tumor burden. Preliminary clinical studies with denosumab, an anti-RANKL fully human monoclonal antibody, in patients with solid tumors with bone metastases and myeloma showed that targeting RANKL reduces osteoclastogenesis, bone resorption markers and skeletal-related events, supporting further study of this molecule and others with anti-RANKL activity.
Terpos
Evangelos
E
Alexandra University Hospital, University of Athens School of Medicine, Department of Clinical Therapeutics, 5 Marathonomahon street, Drosia Attikis, 14572, Athens, Greece. eterpos@hotmail.com
Efstathiou
Eleni
E
Christoulas
Dimitrios
D
Roussou
Maria
M
Katodritou
Eirini
E
Dimopoulos
Meletios-Athanassios
MA