Developing an effective gene therapy for prostate cancer: New technologies with potential to translate from the laboratory into the clinic.

Rupesh Dash, Belal Azab, Xue Ning Shen, Upneet K. Sokhi, Siddik Sarkar, Zhao zhong Su, Xiang Yang Wang, Pier Paolo Claudio, Paul Dent, Igor P. Dmitriev, David T. Curiel, Steven Grant, Devanand Sarkar, Paul B. Fisher

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)46-56
Number of pages11
JournalDiscovery medicine
Volume11
Issue number56
StatePublished - Jan 1 2011
Externally publishedYes

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