Androgen receptor modulation: lessons learned from beyond the prostate.
Androgen receptor (AR) is an important transcription factor in prostatic diseases, such as prostate cancer and benign prostatic hyperplasia (BPH). AR regulates the growth and survival of both benign and cancerous prostate epithelial cells. Therefore, modulation of AR function is an important means of treating prostatic diseases. Modern pharmacotherapy for these diseases includes, for example, medical castration and AR antagonists for prostate cancer and 5-alpha-reductase inhibitors for BPH. However, these treatments have limitations and are illustrated by AR reactivation after medical castration for prostate cancer, commonly termed castrate-resistant prostate cancer. A novel method of AR modulation has been demonstrated in spinal and bulbar muscular atrophy, a disease defined by a polyglutamine repeat expansion which leads to gain-of-function changes in AR and neuromuscular pathology. Here, we examine recent findings from the description of a compound that degrades AR and induces dissociation of AR from an AR coactivator. The biochemistry of this compound may have implications for prostate cancer.
Sharifi
Nima
N
Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. nima.sharifi@nih.gov
Figg
William D
WD
D000728:Androgens / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D008024:Ligands; D008297:Male; D010455:Peptides / Q000737:chemistry; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology*; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion
C410798:AR protein, human; D000728:Androgens; D008024:Ligands; D010455:Peptides; D011944:Receptors, Androgen; C097188:polyglutamine; D013739:Testosterone