%0 Journal Article
%T Biomarker-Based Targeting of the Androgen-Androgen Receptor Axis in Advanced Prostate Cancer
%A Manish Kohli
%A Rui Qin
%A Rafael Jimenez
%A Scott M. Dehm
%J Advances in Urology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/781459
%X Recent therapeutic advances for managing advanced prostate cancer include the successful targeting of the androgen-AR axis with several new drugs in castrate resistant prostate cancer including abiraterone acetate and enzalutamide (MDV3100). This translational progress from ¡°bench to bed-side¡± has resulted in an enlarging repertoire of novel and traditional drug choices now available for use in advanced prostate cancer therapeutics, which has had a positive clinical impact in prolonging longevity and quality of life of advanced prostate cancer patients. In order to further the clinical utility of these drugs, development of predictive biomarkers guiding individual therapeutic choices remains an ongoing challenge. This paper will summarize the potential in developing predictive biomarkers based on the pathophysiology of the androgen-AR axis in tumor tissue from patients with advanced prostate cancer as well as inherited variation in the patient¡¯s genome. Specific examples of rational clinical trial designs incorporating potential predictive biomarkers from these pathways will illustrate several aspects of pharmacogenetic and pharmacogenomic predictive biomarker development in advanced prostate cancer therapeutics. 1. Introduction Prostate cancer (PCa) is the second leading cause of cancer-related mortality in US men with an estimated 33,720 deaths in 2011 [1]. Virtually all PCa-related deaths occur in patients with metastatic-stage disease, the initial treatment for which is androgen deprivation therapy (ADT) [2, 3]. In addition to advanced metastatic stage disease, ADT has also been used for treating locally advanced PCa and for biochemically relapsed disease after failure of localized-stage treatments with radical prostatectomy or radiation therapy. It has been estimated that a third of the over 2.3 million men with PCa in the US received ADT in 2007 as part of their care [4]. ADT therefore constitutes a significant clinical therapy for PCa patients. However, while it provides effective control of disease for variable time periods [5¨C8] in metastatic PCa patients, ADT also contributes to side effects including osteoporosis, loss of sexual libido, increased risk of diabetes and coronary artery disease, and metabolic syndrome [9]. Several challenges therefore remain in the use of ADT in PCa. Foremost is the lack of validated biomarkers predictive of treatment response to ADT or side effects of ADT which can be incorporated into designing clinical trials that optimize ADT treatment effects. Since the physiological basis of ADT action is to block the
%U http://www.hindawi.com/journals/au/2012/781459/