RANKL inhibition in the treatment of bone metastases.
OBJECTIVE
Bone metastases are common in patients with advanced malignancies and are associated with skeletal-related events, cancer progression, and death. Receptor activator of nuclear factor kappa beta ligand (RANKL) and its receptor, RANK, key mediators of osteoclast differentiation and function, play a pivotal role in bone destruction induced by metastatic bone tumors. The present review summarizes the contribution of RANKL to pathologic bone disease and presents early clinical data on RANKL inhibition in human metastatic cancer.


RESULTS
RANKL/RANK interactions are essential for normal bone homeostasis. Binding of RANKL to RANK induces osteolytic bone resorption, a process that occurs in excess when tumor cells are present in bone. In cancer patients, increased tumor-induced osteolysis that is measurable using bone resorption markers can be used to monitor response to treatment or predict tumor progression. Denosumab, a novel, fully human monoclonal antibody specific to RANKL, suppresses bone resorption markers in patients with a variety of metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases.


CONCLUSIONS
RANKL is an appropriate target to reduce the osteolytic bone damage caused by bone metastases. Clinical trials are ongoing to assess the safety and efficacy of denosumab for the treatment of bone resorption in patients with metastatic cancers.
Lipton
Allan
A
Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, USA. alipton@psu.edu
Jun
Susie
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary; D016723:Bone Remodeling; D001862:Bone Resorption / Q000503:physiopathology; D002986:Clinical Trials as Topic; D000069448:Denosumab; D006801:Humans; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000069448:Denosumab