Current curative strategies for prostate cancer are restricted to the primary tumour, and the effect of treatments to control metastatic disease is not sustained. Therefore, the application of gene therapy to prostate cancer is an attractive alternative.
Baculoviruses are highly restricted insect viruses, which can enter, but not replicate in mammalian cells. Baculoviruses can incorporate large amounts of extra genetic material, and will express transgenes in mammalian cells when under the control of a mammalian or strong viral promoter. Successful gene delivery has been achieved both in vitro and in vivo and into both dividing and nondividing cells, which is important since prostate cancers
divide relatively slowly. In addition, the envelope protein gp64 is sufficiently mutable to allow targeted transduction of particular cell types. In this review, the advantages of using
baculoviruses for prostate cancer gene therapy are explored, and the mechanisms of viral entry and transgene expression are described.
Gene therapy is rapidly emerging as a viable clinical strategy to treat prostate cancer. New developments, such as targeted expression of therapeutic genes, and viruses that are designed to selectively replicate in prostate cancer cells have led to vectors with improved safety, even in elderly male patients. This review describes the various different viral and non-viral strategies employed to date, with a summary of current clinical trials. The main focus of the review is a discussion of the need, and the potential methods that can be used for targeted expression of the therapeutic gene specifically to prostate tumours and metastases. This includes methods of abrogating vector transduction of non-specific tissues, enhancement of transduction into prostate tumour tissue, transcriptional control of the therapeutic gene and some examples of prostate cancer-specific therapeutic genes. We also consider the future of prostate cancer gene therapy and the factors that should be taken into account when designing clinical trials, in a field that is expected to impact on clinical management of a common tumour type.
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