GTMB 7 - Gene Therapy & Molecular Biology

Gene Therapy and Molecular Biology Vol 7, page 113Gene Ther Mol Biol Vol 7, 113-133, 2003Current progress in adenovirus mediated genetherapy for patients with prostate carcinomaReview ArticleAhter D. Sanlioglu 1,3 , Turker Koksal 2,3 , Mehmet Baykara 2,3 , Guven Luleci 1,3 , BahriKaracay 4 and Salih Sanlioglu 1,3, *1 Departments of Medical Biology and Genetics, 2 Department of Urology and 3 The Human Gene Therapy Unit of AkdenizUniversity, Faculty of Medicine, Antalya, Turkey, 07070; 4 Department of Pediatrics, University of Iowa, College ofMedicine, Iowa City, IA, 52240, USA__________________________________________________________________________________*Correspondence: Salih Sanlioglu V.M.D., Ph.D., Director of The Human Gene Therapy Unit of Akdeniz University, Faculty ofMedicine, B- Block, 1 st floor, Campus, Antalya, 07070 Turkey; Phone: (90) 242-227-4343/ext: 44359, Fax: (90) 242-227-4482; e-mail:sanlioglu@akdeniz.edu.trKey words: Prostate cancer, adenovirus, gene therapy, immunomodulation, apoptosis, inducible promotersReceived: 1 July 2003; Accepted: 11 July 2003; electronically published: July 2003SummaryProstate cancer is the most frequently diagnosed male cancer in the world. Like all cancers, prostate cancer is adisease of uncontrolled cell growth. In some cases tumors are slow growing and remain local, but in others they mayspread rapidly to the lymph nodes, other organs and especially bone. Although surgery and radiation can cure earlystages of organ confined prostate carcinoma (stages I and II), there is no curative therapy at this time for locallyadvanced or metastatic disease (stages III and IV). The likelihood of postsurgical local recurrence increases withcapsular penetration as detected in 30 % of the patients at the time of radical prostatectomy. Moreover, 10-15 % ofpatients have metastatic cancer at the time of diagnosis. Considering the fact that 60 % local recurrence is observedin patients receiving radiation therapy with or without adjuvant hormonal ablation therapy, it is generally believedthat androgen ablation therapy simply delays the progression of prostate carcinoma to a more advanced stage. Inaddition, the overall ten-year survival rate of patients with locally recurrent prostate cancer is only around 35 %;thus; the ultimate progression into androgen independent prostate carcinoma appears to be inevitable. Genetherapy arose as a novel treatment modality with the potential to decrease the morbidity associated withconventional therapies. Therefore, gene therapy is expected to lower the incidence of tumor recurrence and finallyimprove the outcome of patients with recurrent and androgen independent prostate carcinoma. Viral vectors aremost commonly used for the purpose of gene therapy. Currently, there are a total of 40 clinical trials beingconducted using viral vectors for the treatment of prostate carcinoma. 22 out of 40 clinical protocols (55 %)approved for the treatment of prostate cancer utilize adenovirus vectors. Most of these adenovirus mediatedtherapeutic approaches employ either selectively replicating adenoviruses or suicide gene therapy approaches. Inthis review, we mainly concentrated on the progress in adenovirus mediated gene therapy approaches for prostatecancer. Analysis of the death ligand mediated gene therapy approach was also discussed in detail, while our novelfindings were incorporated as an example for up-to-date approaches used for adenovirus mediated gene therapyagainst prostate carcinoma.I. IntroductionProstate cancer is the second leading cause of deathin men from cancer following lung carcinoma with anannual mortality rate of 38,000 (Yeung and Chung, 2002).There are 200,000 newly diagnosed cases of prostatecarcinoma every year in the United States alone (Boring etal, 1994; Greenlee et al, 2001). As a result, prostatecarcinoma is claimed to be the most frequently diagnosedmale cancer in the United States (Powell et al, 2002).Despite the fact that there has been a considerable effortfor screening and early detection of prostate cancer inrecent years, the lifetime risk of being diagnosed withprostate cancer is still reported to be 1 in 5 (Grumet andBruner, 2000). Several hundred clinical studies usingexperimental or approved chemotherapeutics failed toimprove survival rates of patients with prostate cancer(Devi, 2002). Because prostate cancer is a heterogeneous113