New prospectives of prostate cancer gene therapy: molecular targets and animal models.
Prostate cancer is the most common cancer and the second leading cause of cancer-related death among North American men. The low cure rate for prostate cancer is associated with the fact that many patients have metastatic disease at the time of disease presentation. Currently available therapeutic modalities for prostate cancer, such as surgery, radiation, hormone therapy, and chemotherapy, have failed to cure patients because these therapies are not sufficiently tumor-specific, resulting in dose-limiting toxicity. Therefore, gene therapy may offer great promise in this regard. In this article, we summarize current advances in gene therapy technologies for the treatment of cancer in general, and future prospects for treatment of human prostate cancer metastasis. We specifically emphasize current studies for improvement, both in the efficiency and the specificity of viral and nonviral vectors, and restricted transgene expression in tumors, to achieve selective targeting with minimized host organ toxicity, based on the molecular understanding of potential regulatory differences between normal and tumor cells. Cell and animal models used to study prostate cancer growth, invasion, and metastasis, and their usefulness in preclinical evaluation of therapeutic vectors in the treatment of prostate cancer skeletal metastasis are also discussed.
Hsieh
C L
CL
Department of Urology, University of Virginia School of Medicine, Charlottesville 22908, USA.
Chung
L W
LW
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D017500:Adenovirus E1A Proteins / Q000502:physiology; D000818:Animals; D019470:Biolistics; D019496:Cancer Vaccines / Q000627:therapeutic use; D002453:Cell Cycle / Q000235:genetics; D003131:Combined Modality Therapy; D016207:Cytokines / Q000627:therapeutic use; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000627:therapeutic use; D003713:Dendritic Cells / Q000637:transplantation; D004337:Drug Carriers; D005544:Forecasting; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007128:Immunoglobulin Fragments / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods; D015552:Injections, Intralesional; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016337:RNA, Catalytic / Q000627:therapeutic use; D051381:Rats; D014183:Transplantation, Heterologous
D017500:Adenovirus E1A Proteins; D019496:Cancer Vaccines; D016207:Cytokines; D004274:DNA, Recombinant; D004337:Drug Carriers; D007128:Immunoglobulin Fragments; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic