Alavi J B, Eck S L
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
Hematol Oncol Clin North Am. 1998 Jun;12(3):617-29. doi: 10.1016/s0889-8588(05)70011-3.
Malignant gliomas are attractive targets for gene therapy because of their relatively well-localized distribution. Several new strategies have been devised that target different aspects of glioma biology. Gene transfer can be used to synthesize chemotherapy drugs that block DNA synthesis within these highly mitotic tumors. New genes can be introduced that restore the functions of mutated tumor suppressor genes or block the molecular pathways needed for tumor angiogenesis. Alternatively, the immune response to these tumors can be augmented by the local production of cytokines. Finally, viruses themselves can be used as tumoricidal agents by designing viruses that selectively replicate and destroy tumor cells. The advantages and limitations of these approaches are discussed in the context of their possible application to the treatment of these highly lethal malignancies.
恶性胶质瘤因其相对局限的分布而成为基因治疗的理想靶点。已经设计出了几种针对胶质瘤生物学不同方面的新策略。基因转移可用于合成化疗药物，这些药物能阻断这些高增殖性肿瘤内的DNA合成。可以引入新基因来恢复突变的肿瘤抑制基因的功能，或阻断肿瘤血管生成所需的分子途径。此外，通过局部产生细胞因子可增强对这些肿瘤的免疫反应。最后，通过设计能选择性复制并破坏肿瘤细胞的病毒，病毒本身也可作为杀瘤剂。这些方法的优缺点将在其可能应用于治疗这些高度致命性恶性肿瘤的背景下进行讨论。
