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晚期癌症中的血管生成抑制剂。许多当前的临床试验显示出了有前景的结果。

[Angiogenesis inhibitors in advanced cancer. Many current clinical trials show promising results].

作者信息

Christofferson R

机构信息

Barnkirurgiska sektionen, Akademiska barnsjukhuset, Uppsala.

出版信息

Lakartidningen. 1998 May 13;95(20):2349-54.

PMID:9630803
Abstract

Tumour growth and metastasis are dependent on angiogenesis, the formation of new blood vessels. In experimental models, tumour regression can be induced by the administration of specific angiostatic agents. The inhibition of angiogenesis represents a new approach in cancer therapy. Specific inhibition of angiogenesis is not characterised by the typical dose-limiting toxicity of chemotherapy. By targeting the untransformed and genetically stable vascular endothelium, drug delivery is no problem, and angiostatic therapy is not associated with the development of drug resistance. However, the treatment has to be continued for months or years, and some angiostatic agents are known to interfere with fertility. Approximately thirty angiostatic agents are undergoing clinical trials, and another fifty agents preclinical testing. Since the clinical trials are performed on patients with advanced tumours intractable to conventional therapy, and as the test drugs are first generation angiostatic agents, their effect is measured in terms of delay in tumour progression or reduction in values for surrogate endpoints such as tumour markers. In this article, based on reports presented at a recent international conference on angiogenesis antagonists, a few angiostatic agents are reviewed with brief comments on their performance in early clinical trials, and some new and promising angiostatic strategies are outlined.

摘要

肿瘤的生长和转移依赖于血管生成,即新血管的形成。在实验模型中,给予特定的血管生成抑制因子可诱导肿瘤消退。抑制血管生成是癌症治疗的一种新方法。特异性抑制血管生成的特点不是化疗典型的剂量限制性毒性。通过靶向未转化且基因稳定的血管内皮,药物递送不成问题,并且血管生成抑制疗法与耐药性的产生无关。然而,治疗必须持续数月或数年,并且已知一些血管生成抑制因子会干扰生育能力。大约有30种血管生成抑制因子正在进行临床试验,另有50种正在进行临床前测试。由于临床试验是在对传统治疗难以治愈的晚期肿瘤患者身上进行的,并且由于受试药物是第一代血管生成抑制因子,其效果是根据肿瘤进展的延迟或替代终点值(如肿瘤标志物)的降低来衡量的。在本文中,基于最近一次关于血管生成拮抗剂的国际会议上发表的报告,对一些血管生成抑制因子进行了综述,并对它们在早期临床试验中的表现作了简要评论,同时概述了一些新的、有前景的血管生成抑制策略。

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