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The androgen receptor plays a major role in the development and function of normal and malignant prostate cells. Due to the relationship of the androgen receptor and prostatic growth, it has been proposed that polymorphisms within the androgen receptor may play a role in an individual’s susceptibility to developing prostate cancer. An inverse relationship has been established between a highly polymorphic trinucleotide repeat located in the first exon of the androgen receptor and the transactivaton function of the receptor. Serum samples were collected from 131 patients with histologically confirmed adenocarcinoma of the prostate, DNA was isolated, and the polymorphic CAG repeat was amplified by PCR and sequenced. The CAG repeat lengths were then compared with age at diagnosis, age at time of study, baseline log[sub 10] PSA, Gleason score, time from diagnosis to initiation of hormonal therapy, time to progression after androgen ablation, and overall survival time. No correlation was found between CAG length and time to progression or overall survival time, but a significant correlation was found between Gleason score and CAG length suggesting that shorter CAG lengths may predict a higher histological grade of prostate cancer.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Numerous growth-inducing signaling pathways have been implicated in the development of metastatic castrate-resistant prostate cancer, but their cross-talk with androgen receptor functions remains poorly understood. A recent study published in Science Signaling by Chen et al.1 has identified a novel androgen-mediated signaling axis driven by loss of SPDEF and gain of TGFBI to facilitate metastasis, which may explain the acquisition of resistance to androgen deprivation therapy. These findings suggest that therapeutic inhibition of androgen signaling may inadvertently promote castrate resistance by inhibiting tumor suppressive functions of the androgen receptor. [ABSTRACT FROM AUTHOR]

Significant therapeutic progress has been made in treating prostate cancer in recent years. Drugs such as enzalutamide, abiraterone, and cabazitaxel have expanded the treatment armamentarium, although it is not completely clear which of these drugs are the most-effective option for individual patients. Moreover, such advances have been tempered by the development of therapeutic resistance. The purpose of this review is to summarize the current literature pertaining to the biochemical effects of AR variants and their consequences on prostate cancer therapies at both the molecular level and in clinical treatment. We address how these AR splice variants and mutations affect tumor progression and therapeutic resistance and discuss potential novel therapeutic strategies under development. It is hoped that these therapies can be administered with increasing precision as tumor genotyping methods become more sophisticated, thereby lending clinicians a better understanding of the underlying biology of prostate tumors in individual patients. [ABSTRACT FROM AUTHOR]