Prins J, de Vries E G, Mulder N H
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Clin Oncol (R Coll Radiol). 1993;5(4):245-52. doi: 10.1016/s0936-6555(05)80238-9.
Inhibition of oncogenes represents a new strategy that might lead to a better understanding of the different steps involved in tumorigenesis and also to the development of new therapeutic approaches. Attempts have been made to interfere with gene expression by in situ generation of mRNA from recombinant vectors (antisense RNA) or by the exogenous introduction of synthetic oligonucleotides (antisense oligonucleotides). Antisense oligonucleotides can inhibit the expression of specific genes by blocking the translation after hybridization with the target mRNAs--the antisense strategy. Antisense oligonucleotides can also be targeted to specific sequences of the DNA double helix. This causes inhibition of transcription--the antigene strategy. Regulatory sequences involved in controlling the transcription of oncogenes are used as targets for this type of 'antigene' oligonucleotide. Both strategies can be applied to control the oncogene expression of tumour cells in tissue culture, as exemplified in this review by myc antisense oligonucleotides. Recently the antisense strategy is moving into the area of clinical trials, aimed at curing chronic myelogenous leukaemia by ex vivo bone marrow purging. However, many difficulties have still to be overcome before the application of antisense oligonucleotides can be evaluated in the treatment of cancer.
抑制癌基因代表了一种新策略，这可能会让人更好地理解肿瘤发生过程中涉及的不同步骤，也有助于开发新的治疗方法。人们已尝试通过从重组载体原位生成mRNA（反义RNA）或通过外源引入合成寡核苷酸（反义寡核苷酸）来干扰基因表达。反义寡核苷酸可通过与靶mRNA杂交后阻断翻译来抑制特定基因的表达——即反义策略。反义寡核苷酸也可靶向DNA双螺旋的特定序列。这会导致转录抑制——即反基因策略。参与控制癌基因转录的调控序列被用作这类“反基因”寡核苷酸的靶点。这两种策略均可用于在组织培养中控制肿瘤细胞的癌基因表达，本综述中以myc反义寡核苷酸为例进行了说明。最近，反义策略正进入临床试验领域，旨在通过体外骨髓净化来治愈慢性粒细胞白血病。然而，在评估反义寡核苷酸在癌症治疗中的应用之前，仍有许多困难需要克服。
