Gene therapy for prostate cancer; Development of tissue specific promoter-based gene therapy

We have defined the androgen responsiveness and status of prostate specific antigen (PSA) secretion of prostate cancer cells as well as non-prostatic cells transduced with PSA promoter reporter constructs. Androgen-independent (Al) human prostate cancer remains a lethal phenotype for which there is no effective therapy. AI prostate cancer produces and secretes large amounts of PSA at both primary and metastatic sites. The aim of this investigation is to explore the use of the PSA promoter as a mean of prostate cell specific expression of a toxic gene thymidine kinase (TK) to an AI PSA-producing human prostate cancer cell line. An adenovirus vector carrying human herpes simplex thymidine kinase (TK) gene under control of the PSA promoter (Ad-PSA-TK) was generated to target PSA-producing Al prostate cancer cells. Upon the administration of acyclovir, Ad-PSA-TK efficiently killed the AI PSA-producing human prostate cancer cells. This paper discusses the importance of tissue specific promoter system,for using gene therapy of prostate cancer, and summarizes recent gene therapy strategies developed to target this process. This strategy can potentially be used in combination with current therapeutic modalities to achieve more effective tumor cell-kill with much reduced toxicity.