Gene therapy of prostate cancer: p53, suicidal genes, and other targets.
Prostate tumor initiation and progression to malignancy may involve upregulation of the androgen receptor known to stimulate prostate cell proliferation; other etiologic mechanisms may include dysfunction of the apoptotic pathway but also deregulation in signal transduction and control of the cell cycle in prostate tissue; such abnormalities could arise from overexpression or mutations in a number of oncogenes or down-regulation by inactivating mutations, allelic loss, or other epigenetic mechanisms in tumor suppressor genes. The advantages and drawbacks of various delivery systems (retroviral, adenoviral, liposomes) used for human gene therapy are being considered. Several ex vivo and in vivo as well as cell culture studies are suggested for the therapy of the human prostate cancer using transfer and expression of genes that might be implicated in prostate carcinogenesis especially of the tumor suppressor p53. Expression of suicidal genes in prostate cancer cells using prostate-specific promoter and enhancer elements as well as targeting of the androgen receptor or the insulin-like growth factor genes with triplex technology in prostate cancer cells and their metastases, is expected to be of therapeutic value.
Boulikas
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Institute of Molecular Medical Sciences, Palo Alto, California 94306, USA.
D000728:Androgens / Q000502:physiology; D017209:Apoptosis; D002453:Cell Cycle; D005260:Female; D018014:Gene Transfer Techniques; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D012190:Retroviridae; D015398:Signal Transduction
D000728:Androgens