Pierga J Y, Magdelenat H
Laboratoire de Physiopathologie, Institut Curie, Paris, France.
Cell Mol Biol (Noisy-le-grand). 1994 May;40(3):237-61.
The identification of genes that confer a growth advantage to tumoral cells and the knowledge of the genetic mechanisms responsible for their activation have made possible a direct genetic approach to cancer treatment by nucleic acid as therapeutical agents. Antisense oligonucleotides (oligos) can be designed to complement a region of a particular gene or messenger RNA and serve as potential blockers of transcription or translation through sequence-specific hybridization. Inhibition of gene expression using oligos has been demonstrated in variety of in vitro models in oncology. Much more rare are actual effects in animal models and clinical trials are just being sketched. The ability of these compounds to access the biological target is critical. Rigourous demonstration of their in vivo effects and favourable pharmacological properties is mandatory before being used as therapeutical agents.
鉴定赋予肿瘤细胞生长优势的基因以及了解负责其激活的遗传机制，使得通过核酸作为治疗剂对癌症治疗采用直接的基因方法成为可能。反义寡核苷酸（oligos）可以设计成与特定基因或信使RNA的一个区域互补，并通过序列特异性杂交作为转录或翻译的潜在阻断剂。在肿瘤学的各种体外模型中，已经证明使用寡核苷酸抑制基因表达。在动物模型中的实际效果要罕见得多，而临床试验才刚刚起步。这些化合物到达生物靶点的能力至关重要。在用作治疗剂之前，必须严格证明它们的体内效果和良好的药理学特性。
