%0 Journal Article
%T Bone-Targeted Therapies in Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms
%A Joelle El-Amm
%A Ashley Freeman
%A Nihar Patel
%A Jeanny B. Aragon-Ching
%J Prostate Cancer
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/210686
%X 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. 1. Introduction Prostate cancer remains the most common noncutaneous cancer among American men [1]. More than 90% of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in a significant increase in the risk of morbidity and mortality [2, 3]. The extent of bone involvement in mCRPC has been also found to be associated with patient survival [4]. While most patients are clinically asymptomatic, those with symptoms may manifest with either pain or as skeletal-related events (SREs). SREs are defined variably but typically include manifestations of spinal cord compression, pathological fractures, hypercalcemia of malignancy, requirement for interventions such as bone surgery, or need for bone radiation. Historically, in the absence of bone-targeted therapy, the rate of SREs at 15 months was reported to be 44%, including a 22% rate of fracture [5, 6]. While the mechanisms and lesions in mCRPC have traditionally been thought of as osteoblastic, increasing evidence lends credence to the importance of osteolytic and proosteoclastogenic factors in prostate cancer metastases, which brings about evidence of both an osteolytic and an osteoblastic component with increased bone formation and resorption [7]. Docetaxel, the standard first-line chemotherapy agent in mCRPC, not only improves
%U http://www.hindawi.com/journals/pc/2013/210686/