Kohli Manish, Qin Rui, Jimenez Rafael, Dehm Scott M
Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Adv Urol. 2012;2012:781459. doi: 10.1155/2012/781459. Epub 2012 Aug 22.
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.
晚期前列腺癌治疗的最新进展包括，在去势抵抗性前列腺癌中成功使用几种新药靶向雄激素 - AR轴，这些新药包括醋酸阿比特龙和恩杂鲁胺（MDV3100）。从“ bench到bed - side”的这一转化医学进展，使得晚期前列腺癌治疗中可供使用的新型和传统药物选择不断增加，这对延长晚期前列腺癌患者的寿命和提高生活质量产生了积极的临床影响。为了进一步提高这些药物的临床效用，开发指导个体治疗选择的预测性生物标志物仍然是一项持续的挑战。本文将总结基于晚期前列腺癌患者肿瘤组织中雄激素 - AR轴的病理生理学以及患者基因组中的遗传变异来开发预测性生物标志物的潜力。纳入来自这些途径的潜在预测性生物标志物的合理临床试验设计的具体实例，将说明晚期前列腺癌治疗中药理学和药物基因组学预测性生物标志物开发的几个方面。
