文章：

血管生成抑制剂的临床转化

Clinical translation of angiogenesis inhibitors

原文发布日期：2002-10-01

DOI: 10.1038/nrc905

类型: Review Article

开放获取: 否

要点：

1. Angiogenesis inhibitors are a relatively new class of cancer drugs. The biological and biochemical characteristics of angiogenesis inhibitors, however, differ from conventional cytotoxic chemotherapy.
2. Basic research into the angiogenic process has revealed several ways by which the clinical efficacy of angiogenesis inhibitors can be improved. These include:
3. Differentiating between direct and indirect angiogenesis inhibitors.
4. Realizing that the microvascular endothelial cell is a genetically stable target of anti-angiogenic therapy.
5. Understanding that slowly growing tumours, which are more difficult to treat by chemotherapy, respond well to anti-angiogenic therapy.
6. An appreciation that rapidly growing tumours require higher doses of an angiogenesis inhibitor.
7. Angiogenesis inhibitors are most effective when administered on a dose-schedule that maintains a constant concentration in the circulation instead of a schedule in which therapy is periodically discontinued. Chemotherapy seems to be angiogenesis dependent, in part, and a change in schedule to optimally target the endothelial cell instead of the tumour cell can overcome drug resistance in tumour-bearing mice.
8. A current unsolved problem in anti-angiogenic therapy is the lack of surrogate markers for therapeutic efficacy. Whether quantification of circulating progenitor endothelial cells will become an indicator of efficacy remains to be shown.
9. When various angiogenesis inhibitors become available for clinical use in cancer patients, these new therapeutic agents might be added to chemotherapy or to radiotherapy, or used in combination with immunotherapy or vaccine therapy.

要点翻译：

1. 血管生成抑制剂是一类相对较新的抗癌药物。但其生物学和生化特性与传统细胞毒性化疗药物存在差异。
2. 对血管生成过程的基础研究揭示了多种提高血管生成抑制剂临床疗效的途径，包括：
3. 区分直接作用与间接作用的血管生成抑制剂；
4. 认识到微血管内皮细胞是抗血管生成治疗中遗传稳定的靶点；
5. 理解生长缓慢的肿瘤（这类肿瘤对化疗较不敏感）对抗血管生成治疗反应良好；
6. 认识到快速生长的肿瘤需要更高剂量的血管生成抑制剂。
7. 当按照维持循环中恒定药物浓度的给药方案（而非周期性中断治疗的方案）使用时，血管生成抑制剂能达到最佳疗效。化疗在一定程度上依赖于血管生成，通过调整给药方案以最优方式靶向内皮细胞而非肿瘤细胞，可克服荷瘤小鼠的药物耐药性问题。
8. 当前抗血管生成治疗中一个未解决的难题是缺乏疗效替代标志物。循环祖代内皮细胞的定量分析是否会成为疗效指标仍有待证实。
9. 当多种血管生成抑制剂可供癌症患者临床使用时，这些新型治疗药物可与化疗或放疗联用，亦可与免疫治疗或疫苗治疗联合应用。

英文摘要：

Angiogenesis inhibitors are a new class of drugs, for which the general rules involving conventional chemotherapy might not apply. The successful translation of angiogenesis inhibitors to clinical application depends partly on the transfer of expertise from scientists who are familiar with the biology of angiogenesis to clinicians. What are the most common questions that clinicians ask as they begin to test angiogenesis inhibitors in cancer clinical trials?

摘要翻译： 

血管生成抑制剂是一类新型药物，常规化疗的通用规则可能并不适用。将血管生成抑制剂成功转化为临床应用，部分依赖于熟悉血管生成生物学的科学家向临床医生的知识传递。当临床医生开始在癌症临床试验中测试血管生成抑制剂时，他们最常提出的问题是什么？

原文链接：

Clinical translation of angiogenesis inhibitors