Tidd D M
Department of Radiation Oncology, University of Liverpool, Clatterbridge Hospital, Wirral, Merseyside, UK.
Anticancer Res. 1990 Sep-Oct;10(5A):1169-82.
The identification of activated oncogenes as the basic biochemical difference between tumour cells and normal cells has opened up the possibility for development of truly tumour specific chemotherapy. It may be hypothesized that malignant cells would revert to a more normal phenotype and might even be triggered into terminal differentiation if expression of the appropriate oncogenes were inhibited. Although, at present, it is not possible to anticipate what form future therapy based upon this approach would take, it is clear that the immediate priority must be to establish the general validity of the hypothesis with a variety of tumour cell types in vitro. For this purpose antisense oligonucleotide analogues appear to offer considerable promise as sequence specific inhibitors of oncogene expression. However, no analogue structure yet devised fulfils all the requirements of an ideal antisense effector in terms of biological stability, cell uptake, non-toxicity, hybridization efficiency and mechanism of action on target nucleic acids. Inhibition of oncogene expression in certain cell types has been reported using antisense oligonucleotides but the technique is not universally applicable and more detailed biochemical investigations of the interactions of oligonucleotides with intact cells are required before improved structures may be developed.
将激活的癌基因确定为肿瘤细胞与正常细胞之间的基本生化差异，为开发真正具有肿瘤特异性的化疗方法开辟了可能性。可以推测，如果适当的癌基因表达受到抑制，恶性细胞将恢复为更正常的表型，甚至可能被诱导进入终末分化。虽然目前还无法预测基于这种方法的未来治疗将采取何种形式，但很明显，当务之急是在体外使用多种肿瘤细胞类型来确立这一假设的普遍有效性。为此，反义寡核苷酸类似物作为癌基因表达的序列特异性抑制剂似乎具有很大的前景。然而，就生物稳定性、细胞摄取、无毒性、杂交效率以及对靶核酸的作用机制而言，目前设计出的类似物结构都不能完全满足理想反义效应器的所有要求。已经报道了使用反义寡核苷酸抑制某些细胞类型中的癌基因表达，但该技术并非普遍适用，在开发出改进结构之前，需要对寡核苷酸与完整细胞之间的相互作用进行更详细的生化研究。
