Steiner M S, Gingrich J R
Department of Urology, University of Tennessee, Memphis, Tennessee.
J Urol. 2000 Oct;164(4):1121-36.
The ability to recombine specifically and alter DNA sequences followed by techniques to transfer these sequences or even whole genes into normal and diseased cells has revolutionized medical research and ushered the clinicians of today into the age of gene therapy. We provide urologists a review of relevant background information, outline current treatment strategies and clinical trials, and delineate current challenges facing the field of gene therapy for advanced prostate cancer.
We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from national meetings, relevant to gene therapy and advanced prostate cancer. We selected for review literature representative of the principal scientific background for current gene therapy strategies and National Institutes of Health Recombinant DNA Advisory Committee approved clinical trials.
Current prostate cancer gene therapy strategies include correcting aberrant gene expression, exploiting programmed cell death pathways, targeting critical cell biological functions, introducing toxic or cell lytic suicide genes, enhancing the immune system antitumor response and combining treatment with conventional cytotoxic chemotherapy or radiation therapy.
Many challenges lie ahead for gene therapy, including improving DNA transfer efficiency to cells locally and at distant sites, enhancing levels of gene expression and overcoming immune responses that limit the time that genes are expressed. Nevertheless, despite these current challenges it is almost certain that gene therapy will be part of the urological armamentarium against prostate cancer in this century.
特异性重组并改变DNA序列的能力,以及随后将这些序列甚至整个基因转移到正常细胞和患病细胞中的技术,彻底改变了医学研究,并将当今的临床医生带入了基因治疗时代。我们为泌尿外科医生提供相关背景信息的综述,概述当前的治疗策略和临床试验,并阐述晚期前列腺癌基因治疗领域目前面临的挑战。
我们全面回顾了文献,包括来自PubMed和全国会议近期摘要汇编中与基因治疗和晚期前列腺癌相关的内容。我们选择了代表当前基因治疗策略主要科学背景以及美国国立卫生研究院重组DNA咨询委员会批准的临床试验的文献进行综述。
当前前列腺癌基因治疗策略包括纠正异常基因表达、利用程序性细胞死亡途径、靶向关键细胞生物学功能、引入毒性或细胞裂解自杀基因、增强免疫系统抗肿瘤反应以及将治疗与传统细胞毒性化疗或放射治疗相结合。
基因治疗面临许多挑战,包括提高DNA向局部和远处细胞的转移效率、提高基因表达水平以及克服限制基因表达时间的免疫反应。然而,尽管目前存在这些挑战,但几乎可以肯定的是,基因治疗将成为本世纪泌尿外科对抗前列腺癌的武器库的一部分。