Abstract

Abstract The application of dose escalated radiation therapy for localized prostate cancer has a clear therapeutic benefit; however, its clinical use is hampered by the increased risk of damage to surrounding normal tissues. One attractive alternative to elevated doses is radiation sensitizing agents. Prostate cancer cells can be made radiosensitive by targeted reductions of DNA repair proteins via RNA interference. However, without tissue-selective targeting, these agents will also sensitize surrounding tissue, leading to increased adverse effects. Here we describe a strategy where prostate-targeted RNA interference is used to selectively radio-sensitize prostate cancer cells. A high throughput siRNA screen was completed to identify DNA-repair pathway targets for prostate cancer radio-sensitization. Candidate siRNAs were then conjugated to PSMA-targeted RNA aptamers for selective delivery of siRNAs to Prostate cancer cells. In vitro and in vivo data support PSMA and aptamer-specific targeting and gene knock-down. These studies support continued development of this technology as a path to enhance radiotherapeutic outcomes for men with Prostate cancer and it is the first report of targeted, prostate-specific siRNAs for radio-sensitization. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1503.

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