RANKL inhibition in the treatment of bone metastases

Allan Lipton, Susie Jun

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 β 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.

Original languageEnglish (US)
Pages (from-to)197-203
Number of pages7
JournalCurrent Opinion in Supportive and Palliative Care
Volume2
Issue number3
DOIs
StatePublished - Sep 2008

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Cytoplasmic and Nuclear Receptors
Neoplasm Metastasis
Ligands
Bone and Bones
Neoplasms
Bone Resorption
RANK Ligand
Therapeutics
Clinical Trials
Osteolysis
Bone Diseases
Osteoclasts
Homeostasis
Monoclonal Antibodies
Safety

All Science Journal Classification (ASJC) codes

  • Oncology
  • Medicine(all)
  • Critical Care and Intensive Care Medicine
  • Oncology(nursing)

Cite this

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RANKL inhibition in the treatment of bone metastases. / Lipton, Allan; Jun, Susie.

In: Current Opinion in Supportive and Palliative Care, Vol. 2, No. 3, 09.2008, p. 197-203.

Research output: Contribution to journalArticle

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