Androgen Receptor-Mediated Escape Mechanism from Androgen Ablation Therapy

摘要

Too many prostate-cancer treatments, especially those relying on the suppression of androgen, eventually fail to slow the advance of the disease. One explanation for this situation is the absence of any systematic knowledge on the role and function of the androgen receptor (AR) in the course of prostate cancer development. Recent findings indicate that the AR is the key master regulator (transcription factor) that determines disease progression to androgen independence, which ultimately contributes to death from prostate cancer. During the final stage of this grant we have identified a large number of AR occupied regions (ARORs) in PCa cells. Our work suggests that only some ARORs function under the given physiological conditions, utilizing diverse mechanisms. This diversity points to differential regulation of gene expression by the same transcription factor related to the chromatin structure. Thus, we believe that armed with a deeper knowledge of the hormonal and receptor requirements as well as mechanisms associated with prostate cancer growth and expansion, we may be able to develop therapies that prolong lives. Understanding the behavior of the AR, as documented above, is a first step in that quest.