The Role of Intracrine Androgen Metabolism, Androgen Receptor and Apoptosis in the Survival and Recurrence of Prostate Cancer During Androgen Deprivation Therapy

Michael      V. Fiandalo; Wenjie      Wu; James      L. Mohler

Abstract

Prostate cancer (CaP) is the most frequently diagnosed cancer and leading cause of cancer death in American men. Almost all men present with advanced CaP and some men who fail potentially curative therapy are treated with androgen deprivation therapy (ADT). ADT is not curative and CaP recurs as the lethal phenotype. The goal of this review is to apply our current understanding of CaP and castration-recurrent CaP (CR-CaP) to earlier studies that characterized ADT and the molecular mechanisms that facilitate the transition from androgen-stimulated CaP to CR-CaP. Reexamination of earlier studies also may provide a better understanding of how more newly recognized mechanisms, such as intracrine metabolism, may be involved with the early events that allow CaP survival after initiation of ADT and subsequent development of CR-CaP.

Keywords: Androgen receptor, "backdoor" pathway, prostate cancer, dihydrotestosterone, intracrine metabolism, apoptosis

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