RANK ligand: Effects of inhibition

Saby George, Andrew Brenner, John Sarantopoulos, Ronald M. Bukowski

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

Receptor activator of nuclear factor κ-light-chain-enhancer of activated B-cells (RANK) and its ligand (RANKL) belong to the tumor necrosis factor (TNF) superfamily. RANK mRNA is expressed widely in bone and bone marrow. It has a significant role in stimulating osteoclast differentiation and maturation, and also in preventing apoptosis. Because osteoclast activity is an important aspect of bone resorption in malignancy, targeting these cells is a good rationale for preventing skeletal-related events in malignancies. Preclinical studies have demonstrated the efficacy of denosumab in preventing bone loss in mice and improving bone mineral density. Denosumab is a fully human monoclonal antibody against RANKL, which has been shown to be effective in reducing signaling via RANK and thus osteoclast activity. It has been demonstrated in large, randomized, phase 3 studies to be effective in preventing fractures and bone loss, and improving the bone mineral density in various cancerous and noncancerous settings. This article reviews the latest evidence of RANKL inhibition and its clinical implications.

Original languageEnglish (US)
Pages (from-to)80-86
Number of pages7
JournalCurrent Oncology Reports
Volume12
Issue number2
DOIs
StatePublished - Mar 8 2010

Keywords

  • Bone metastasis
  • Inhibition
  • Monoclonal antibody
  • Osteoporosis
  • RANK ligand

ASJC Scopus subject areas

  • Oncology

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    George, S., Brenner, A., Sarantopoulos, J., & Bukowski, R. M. (2010). RANK ligand: Effects of inhibition. Current Oncology Reports, 12(2), 80-86. https://doi.org/10.1007/s11912-010-0088-1