Androgen Receptor Deregulation and the Transition to Castration Resistance in Prostate Cancer: Mechanisms and Potential Therapeutic Implications

摘要

Prostate cancers of all stages remain exquisitely dependent on the activity of the androgen receptor (AR). Ablation of AR activity is the first line of treatment for non-organ-confined tumors; however, recurrent, castration-resistant prostate cancer (CRPC) emerges for which no effective therapy has been identified. It is well accepted that a significant fraction of CRPCs arise due to recurrent AR activation despite the maintenance of hormone therapy.1 As has been extensively reviewed, means of AR reactivation in CRPCs can be loosely classified into mechanisms that (1) impinge directly on AR modulation; (2) involve alterations in AR cofactors; or (3) promote intratumor ligand synthesis (Fig. 1).