Favrot M, Coll J L, Louis N, Negoescu A
Lung Cancer Research Group, Institut Albert Bonniot, Faculté de Médecine, Université Joseph Fourier, Grenoble, France.
Gene Ther. 1998 Jun;5(6):728-39. doi: 10.1038/sj.gt.3300661.
This review provides a critical evaluation of the increasing use of gene therapy in the treatment of malignancies to induce active cell death (ACD, apoptosis). This approach is consistent with the notion that cancer is an anomalous accumulation of cells largely resulting from diminished cell death. The review details the main genes potentially useful for therapy. Among these, p53 has received the majority of the investigators' attention and provided encouraging results. Even greater hope is offered by newly tried direct inducers of apoptosis, such as bax, bclXs and caspases. Another fruitful direction is the association of apoptosis-inducing gene transfer with radio- and chemotherapy, which are also inducers of ACD. There is a delicate balance between cell gain through mitosis and cell loss in neoplasia because spontaneous apoptosis is widely present in tumors. In fact, the tumor environment favors bystander cell killing which appears to be a fundamental mechanism insofar as the rate of observed cell mortality cannot be accounted for by the known methods of gene transduction with efficiencies far below 100%. We conclude that apoptosis offers a mainstream approach for cancer gene therapy since ACD is highly inducible and only limited gains in malignant cell apoptosis may displace tumors from growth to regression.
本综述对基因疗法在恶性肿瘤治疗中诱导细胞主动死亡（ACD，即凋亡）的应用日益增加进行了批判性评估。这种方法与癌症是主要由细胞死亡减少导致的细胞异常积聚这一观点相一致。该综述详细介绍了可能对治疗有用的主要基因。其中，p53受到了大多数研究者的关注并取得了令人鼓舞的结果。新尝试的凋亡直接诱导剂，如bax、bclXs和半胱天冬酶，带来了更大的希望。另一个富有成效的方向是将诱导凋亡的基因转移与放疗和化疗相结合，放疗和化疗也是ACD的诱导剂。在肿瘤形成过程中，通过有丝分裂的细胞增殖与细胞丢失之间存在微妙的平衡，因为肿瘤中广泛存在自发凋亡。事实上，肿瘤环境有利于旁观者细胞杀伤，这似乎是一个基本机制，因为观察到的细胞死亡率无法用已知的基因转导方法来解释，其效率远低于100%。我们得出结论，凋亡为癌症基因治疗提供了一种主流方法，因为ACD具有高度可诱导性，而且恶性细胞凋亡仅有限增加就可能使肿瘤从生长转变为消退。
