Developing an Effective Gene Therapy for Prostate Cancer: New Technologies with Potential to Translate from the Laboratory into the Clinic

作者: Upneet K. Sokhi , Belal Azab , Siddik Sarkar , Xue-Ning Shen , Paul Dent

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摘要: Prostate cancer is the second leading cause of cancer-related deaths in men U.S. At present, no single or combination therapy has shown efficacy decreasing disease progression patients with metastatic disease. A potentially viable approach for treating late-stage prostate gene therapy. Adenoviruses (Ad) are most commonly used mode delivery, but progress using this vector been hampered by concerns over safety and practicality viruses including conditionally replicating Ads (CRAds), particularly intravenous inefficiency non-viral transfection techniques. Major challenges effective limited infectivity regular Ad serotype 5 (Ad5) inability to specifically deliver therapeutic directly into diseased tissue without trapping liver elimination immune system. The shortcoming Ad5 mostly attributed a reduction Coxsackie-adenovirus receptors (CAR) on surface cells, which can be mitigated generating tropism-modified permitting CAR-independent infection tumor cells. limitations systemic delivery now overcome novel targeted-delivery such as ultrasound (US) contrast agents (microbubbles) reagents, Ads, recombinant proteins, combined ultrasound-targeted microbubble destruction (UTMD), develop site-specific competent transgenic mouse models. These unique strategies enhancing provide direct path translation from laboratory clinic developing an cancer.

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