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Prostate Cancer
Volume 2013 (2013), Article ID 981684, 12 pages
http://dx.doi.org/10.1155/2013/981684
Review Article

Emerging Molecularly Targeted Therapies in Castration Refractory Prostate Cancer

1Division of Medical Oncology, University of UT Huntsman Cancer Institute, Salt Lake City, Utah 84112, USA
2Department of Internal Medicine, University of UT, Salt Lake City, Utah 84112, USA
3Department of Pathology and ARUP Laboratories, University of UT, Salt Lake City, Utah 84108, USA

Received 31 January 2013; Accepted 10 April 2013

Academic Editor: William L. Dahut

Copyright © 2013 Jesal C. Patel 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

Androgen deprivation therapy (ADT) with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC) and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR) signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700), and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials.