Novel Strategies for Targeting the Androgen-Receptor Axis: PARP1 as a Mediator of Androgen Receptor-Dependent Transcriptional Control

摘要

Prostate cancer (PCa) is the most frequently diagnosed malignancy and the second-leading cause of cancer death for men in the United States. While organ-confined disease can be effectively managed, no durable means of cure exists for advanced, nonorgan-confined PCa. First-line therapeutic intervention for locally advanced disease combines radiotherapy (RT) with androgen-deprivation therapy (ADT), as PCa is exquisitely dependent on the action of the androgen receptor (AR) for cell survival and proliferation. However, relapse is common; recurrent tumors arise in 20% to 30% of patients within only 3 years, and in 40% to 50% of patients after 6 years. Thus, there is a significant need to develop new means for targeting recurrent AR activity in both locally advanced and aggressive castration-resistant PCa (CRPC).