Brounais, B., Ruiz, C., Rousseau, J. et al. (4 more authors) (2008) Novel Anti-Cancer Strategy in Bone Tumors by Targeting Molecular and Cellular Modulators of Bone Resorption. Recent Patents on Anti-Cancer Drug Discovery, 3 (3). pp. 178-186. ISSN 1574-8928
Abstract
Tumor cells alter the balanced process of bone formation and bone resorption mediated respectively by osteoblasts and osteoclasts, leading to the disruption of the normal equilibrium and resulting in a spectrum of osteolytic to osteoblastic lesions. This review will summarize research on molecules that play direct and essential roles in the differentiation and activity of osteoclasts, and the role of these molecules in bone destruction caused by cancer. Results from experimental models suggest that the Receptor Activator of NF-kB Ligand (RANKL), a member of the TNF superfamily is a common effector of bony lesions in osteolysis caused by primary and secondary bone tumors. Therefore, osteoclast represents an attractive target across a broad range of tumors that develop in bone. Elucidation of the mechanisms of RANKL interactions with its activator (RANK) and decoy (osteoprotegerin: OPG) receptors has enable the development of pharmacological inhibitors of RANKL (and of its signalling pathway) which have been recently patented, with potential for the treatment of cancer-induced bone disease. Blocking bone resorption by specific other drugs such as bisphosphonates, inhibitors of cathepsin K (the main enzyme involved in bone resorption mechanisms) or signalling pathways regulating osteoclast differentiation and activation is also a promising target for the treatment of osteolysis associated to bone tumors.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2008 Bentham Science Publishers |
Keywords: | Bone resorption; primary bone tumor; bone metastase; RANKL; bisphosphonate |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 May 2016 15:28 |
Last Modified: | 06 Jun 2016 16:48 |
Published Version: | http://www.ingentaconnect.com/contentone/ben/pra/2... |
Status: | Published |
Publisher: | Bentham Science Publishers |
Refereed: | Yes |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98215 |