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Review
. 2011;16(2):136-45.
doi: 10.1634/theoncologist.2010-0154. Epub 2011 Feb 1.

The role of RANK-ligand inhibition in cancer: the story of denosumab

Daniel Castellano  1 , Juan Manuel Sepulveda, Ignacio García-Escobar, Alfredo Rodriguez-Antolín, Anna Sundlöv, Hernán Cortes-Funes
Affiliations
Review

The role of RANK-ligand inhibition in cancer: the story of denosumab

Daniel Castellano et al. Oncologist. 2011.

Abstract

The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular.

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Conflict of interest statement

Disclosures: Daniel Castellano: None; Juan Manuel Sepulveda: None; Ignacio García-Escobar: None; Alfredo Rodriguez-Antolín: None; Anna Sundlöv: None; Hernán Cortes-Funes: None.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors or independent peer reviewers.

Figures

Figure 1.
Figure 1.
The role of RANK-L in bone formation and resorption. Adapted from Roodman, GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655–1664 with permission. Copyright ©2004 Massachusetts Medical Society. All rights reserved. Abbreviations: BMP, bone morphogenic protein; CSF, colony-stimulated factor; FGF, fibroblast growth factor; IGF, insulin-like growth factor; IL, interleukin; PDGF, platelet-derived growth factor; PTHrP, parathyroid hormone-related protein; RANK, receptor activator of nuclear factor-kappa B; RANKL, receptor activator of nuclear factor-kappa B ligand; TGF, transforming growth factor; TNF-α, tumor necrosis factor-α.
Figure 2.
Figure 2.
Factors implicated in bone resorption (A) and formation (B). Abbreviations: BMP, bone morphogenic protein; CSF, colony-stimulated factor; FGF, fibroblast growth factor; IGF, insulin-like growth factor; PDGF, platelet-derived growth factor; TGF, transforming growth factor; RANKL, receptor activator of nuclear factor-kappa B ligand.
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