Anti-Androgen Receptor RNA Enzyme as a Novel Therapeutic Agent for Prostate Cancer In Vivo

摘要

Prostate cancer is the second leading cause of cancer death among men in the western world. Androgen plays a crucial role in the development and growth of normal prostate gland and prostate cancer. Action of androgen is mediated by an androgen receptor (AR) and the AR exerts androgen-regulated gene expression. Standard therapy relies on androgen ablation to remove or block the action of androgens. This therapy results in a regression of the tumor because most primary tumor cells depend on androgens for growth and programmed cell death. However, most prostate cancers eventually relapse as their tumors progress to androgen-refractory. Studies have indicated that the AR gene amplification and mutations are involved in androgen-refractory tumors. Therefore, blockage of the AR gene expression may provide a new approach to the management of the AR-dependent cancer. We have developed anti-AR RNA enzymes that are able to selectively and specially interact with the AR mRNA and cleave the AR mRNA in vitro. Unlike conventional chemotherapy, the enzymes would have lesser side effects because the compounds selectively destroy only the AR gene. This study proposed is to determine specific efficacy of these enzymes in vivo.