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Prostate Cancer
Volume 2013 (2013), Article ID 210686, 10 pages
http://dx.doi.org/10.1155/2013/210686
Review Article

Bone-Targeted Therapies in Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms

1Division of Hematology/Oncology, Department of Medicine, George Washington University Medical Center, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA
2Department of Medicine, George Washington University Medical Center, Washington, DC 20037, USA

Received 10 June 2013; Accepted 25 July 2013

Academic Editor: William L. Dahut

Copyright © 2013 Joelle El-Amm et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC including strontium and samarium, alpharadin is the first radiopharmaceutical to show significant overall survival benefit. Contemporary therapeutic options including enzalutamide and abiraterone have effects on pain palliation and SREs as well. Other novel bone-targeted agents are currently in development, including the receptor tyrosine kinase inhibitors cabozantinib and dasatinib. Emerging therapeutics in mCRPC has resulted in great strides in preventing one of the most significant sources of complications of bone metastases.