Sikora K
Scand J Gastroenterol Suppl. 1985;117:1-8. doi: 10.3109/00365528509092223.
The central problem in cancer therapy is the poor selectivity of current systemic agents against the common solid tumours. The demonstration that unique segments of DNA, constant in location and conserved in evolution are involved in growth control opens new avenues for basic and clinical research. The functions of the products of these genes need to be elucidated. Examples of growth control functions include homology to growth factors, surface receptors, protein kinases and cell cycle control proteins. From DNA sequence data peptides predicted to be exposed within intact molecules can be constructed and used to produce monoclonal antibodies to oncogene products. Such antibodies have now been successfully used to demonstrate the intracellular localisation of gene products as well as the cell cycle regulatory role of the c-myc protein. By having a battery of antibodies against the different gene products their direct clinical application for diagnosis and prognosis has become a reality. Immunohistology and flow cytometry permit the geographical and quantitative analysis of function in normal and neoplastic tissues. Furthermore, by purification and biochemical analysis the molecular basis for their action can be elucidated. It is likely that by the end of the decade new drugs that inhibit oncoprotein function will be available for clinical trial.
癌症治疗的核心问题在于当前全身用药对常见实体瘤的选择性较差。有证据表明,在位置上恒定且在进化过程中保守的独特DNA片段参与生长控制,这为基础研究和临床研究开辟了新途径。这些基因产物的功能需要阐明。生长控制功能的例子包括与生长因子、表面受体、蛋白激酶和细胞周期控制蛋白的同源性。根据DNA序列数据,可以构建预测在完整分子中暴露的肽,并用于生产针对癌基因产物的单克隆抗体。此类抗体现已成功用于证明基因产物的细胞内定位以及c-myc蛋白的细胞周期调节作用。通过拥有一系列针对不同基因产物的抗体,它们在诊断和预后方面的直接临床应用已成为现实。免疫组织学和流式细胞术可对正常组织和肿瘤组织中的功能进行定位和定量分析。此外,通过纯化和生化分析,可以阐明其作用的分子基础。到本十年末,抑制癌蛋白功能的新药可能会用于临床试验。