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The current description of the function of the human androgen receptor (AR), as a transcription factor directing androgen responsive gene expression, is limited in scope and thus is unable to account for the varied cellular and physiological transformation observed in the development and progression of prostate cancer (CaP). The chapter will focus on four important aspects of AR and CaP investigations: (1) a description of AR somatic mutations and the perils of AR-directed therapeutics; (2) our characterization of AR protein interactors that have imbued new functional properties for AR linked to prostatic disease; (3) review of the advances made and shortcomings of AR mouse models in describing CaP onset and progression; and (4) speculate as to the mechanisms by which new mutations can originate and initiate disease onset.

Redefining Androgen Receptor Function: Clinical Implications in Understanding Prostate Cancer Progression and Therapeutic Resistance