RANKL inhibition in the treatment of bone metastases.

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Lipton A, Jun S

RANKL inhibition in the treatment of bone metastases.

Curr Opin Support Palliat Care. 2008 Sep;2(3):197-203. doi: 10.1097/SPC.0b013e32830baac2.

PubMed ID

18685421 [ View in PubMed

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Abstract

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Denosumab	Tumor necrosis factor ligand superfamily member 11	Protein	Humans	Yes	Antibody	Details