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The transcriptional programme of the androgen receptor ( AR ) in prostate cancer
Author(s) -
Lamb Alastair D.,
Massie Charlie E.,
Neal David E.
Publication year - 2014
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.12415
Subject(s) - enzalutamide , androgen receptor , prostate cancer , chromatin immunoprecipitation , cancer research , androgen , transcription factor , biology , receptor , endocrinology , androgen receptor antagonists , testosterone (patch) , medicine , cancer , chemistry , hormone , promoter , gene , gene expression , biochemistry
The androgen receptor ( AR ) is essential for normal prostate and prostate cancer cell growth. AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone. Current molecular techniques, such as chromatin‐immunoprecipitation sequencing (ChIP‐seq), have permitted identification of direct AR ‐binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC. The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide ( MDV3100 , potent AR antagonist), in treating advanced prostate cancer underlines the on‐going critical role of the AR throughout all stages of the disease. Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co‐factors, such as the E2F family, c‐ Myc and signal transducer and activator of transcription ( STAT ) transcription factors. Further treatment approaches must target these other factors.