Benouchan Malika, Colombo Bruno M
UPRES 2360, School of Medicine, Bobigny, France.
Int J Oncol. 2005 Aug;27(2):563-71.
Acquired drug resistance to chemotherapy is a major problem in the treatment of cancer. After primary surgical intervention, followed by chemotherapy treatments, the majority of patients develop disease recurrence. This is due to tumor cell heterogeneity and genetic instability. In contrast to tumor cells, proliferating host endothelial cells (ECs) are genetically stable and have a low mutational rate. Furthermore, tumor angiogenesis plays an important role in tumor development, vascular invasion and hematogenous metastasis. Thus, anti-angiogenic therapy directed against tumor ECs should, in principle, improve the efficacy of antitumor therapy by inducing little or no drug resistance. We review different therapeutic approaches directed against tumor angiogenesis, showing potent antitumor activity in vitro and in vivo. These strategies involve the inhibition of the expression of proangiogenic molecules, as well as the overexpression of anti-angiogenic molecules by either injection of recombinant proteins or transfer of genes encoding anti-angiogenic molecules. The gene therapy approach based on the gene-directed enzyme prodrug therapy (GDEPT) system, as well as the use of endothelial progenitor cells (EPCs) as angiogenesis-selective gene-targeting vectors, will be further discussed.
获得性化疗耐药是癌症治疗中的一个主要问题。在初次手术干预后，接着进行化疗，大多数患者会出现疾病复发。这是由于肿瘤细胞的异质性和基因不稳定性。与肿瘤细胞不同，增殖的宿主内皮细胞（ECs）基因稳定且突变率低。此外，肿瘤血管生成在肿瘤发展、血管侵袭和血行转移中起重要作用。因此，针对肿瘤内皮细胞的抗血管生成疗法原则上应通过诱导很少或不产生耐药性来提高抗肿瘤治疗的疗效。我们综述了针对肿瘤血管生成的不同治疗方法，这些方法在体外和体内均显示出强大的抗肿瘤活性。这些策略包括抑制促血管生成分子的表达，以及通过注射重组蛋白或转移编码抗血管生成分子的基因来过度表达抗血管生成分子。基于基因导向酶前药疗法（GDEPT）系统的基因治疗方法，以及使用内皮祖细胞（EPCs）作为血管生成选择性基因靶向载体，将进一步讨论。
