Antisense oligonucleotide therapy in urology

被引:28
作者
Kausch, I [1 ]
Böhle, A
机构
[1] Res Ctr Borstel, Dept Immunol & Cell Biol, Borstel, Germany
[2] Med Univ Lubeck, Dept Urol, D-23538 Lubeck, Germany
关键词
urinary tract; urologic neoplasms; oligodeoxynucleotides; antisense; gene expression;
D O I
10.1016/S0022-5347(05)64901-4
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Antisense oligonucleotides are short modified DNA or RNA molecules designed to bind selectively messenger RNA and inhibit synthesis of the encoded protein. In the last 20 years antisense technology has emerged as an exciting and promising strategy, especially for treating cancer. We provide urologists with a contemporary review of relevant background information and outline current treatment strategies and clinical trials of antisense oligonucleotide therapy for urological tumors. Materials and Methods: We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from international meetings, on preclinical and clinical studies of antisense oligonucleotide therapy in urology. Results: Current preclinical antisense strategies in urological cancer research include the inhibition of proliferation and induction of tumor cell differentiation, reversal of immunosuppression by tumor secreted molecules and induction of apoptosis. The use of phosphorothioate oligonucleotides as antisense agents has shown promising results in various preclinical cancer models. In recent and current clinical trials in patients with urological tumors antisense agents targeted against c-raf kinase, protein kinase C-alpha, protein kinase A and bcl-2 are being evaluated. Conclusions: Many compounds have achieved convincing in vitro reduction of target messengerRNA and protein expression. Early clinical trials show safety and mild toxicity at the given doses. Overall the current state of antisense oligonucleotide research described promises a highly productive future for this technology. However, for most medical applications of antisense compounds many obstacles related to nuclease stability, affinity, cellular delivery and specificity remain to be clarified.
引用
收藏
页码:239 / 247
页数:9
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