Curiel D T
Gene Therapy Clinic, The University of Alabama at Birmingham, 1824 6th Ave. South, Birmingham, AL 35294-3300, USA.
Breast Cancer Res. 2000;2(1):45-9. doi: 10.1186/bcr28. Epub 1999 Dec 17.
The gene therapy strategy of mutation compensation is designed to rectify the molecular lesions that are etiologic for neoplastic transformation. For dominant oncogenes, such approaches involve the functional knockout of the dysregulated cellular control pathways provoked by the overexpressed oncoprotein. On this basis, molecular interventions may be targeted to the transcriptional level of expression, via antisense or ribozymes, or post-transcriptionally, via intracellular single chain antibodies (intrabodies). For carcinoma of the breast, these approaches have been applied in the context of the disease linked oncogenes erbB-2 and cyclin D1, as well as the estrogen receptor. Neoplastic revision accomplished in modal systems has rationalized human trials on this basis.
突变补偿的基因治疗策略旨在纠正导致肿瘤转化的分子损伤。对于显性癌基因，此类方法涉及对由过度表达的癌蛋白引发的失调细胞控制途径进行功能敲除。在此基础上，分子干预可通过反义核酸或核酶靶向转录表达水平，或通过细胞内单链抗体（胞内抗体）进行转录后干预。对于乳腺癌，这些方法已应用于与该疾病相关的癌基因erbB-2、细胞周期蛋白D1以及雌激素受体的研究中。在模型系统中完成的肿瘤修正已在此基础上使人体试验合理化。
