血管生成研究:从实验室到临床

Angiogenesis research: from laboratory to clinic.

作者信息

Folkman J

机构信息

Children's Hospital and Harvard Medical School, Boston, Massachusetts.

出版信息

Forum (Genova). 1999 Jul-Dec;9(3 Suppl 3):59-62.

DOI:
Abstract

Accumulating experimental evidence demonstrates that tumour growth and lethality are dependent on angiogenesis. When angiogenesis is inhibited by administering molecules which specifically suppress the growth of vascular endothelial cells, tumours in animals can be limited to a dormant microscopic size where they are essentially harmless. The most recent evidence that vascular endothelial cells exert potent growth control over tumour cells comes from the following studies, i. administration of an angiogenesis inhibitor specific for proliferating vascular endothelium in the tumour bed; ii. optimisation of the dose and schedule of conventional cytotoxic chemotherapy for the vascular endothelium; iii. targeting of low dose cytotoxic chemotherapy only to the vascular endothelium in the tumour bed; or iv. sensitisation of vascular endothelium in the tumour bed to radiotherapy by co-administration of an angiogenesis inhibitor. In the future, anti-angiogenic therapy may be added to conventional chemotherapy, radiotherapy, immunotherapy or other novel modalities such as gene therapy. Also, angiogenesis inhibitors may be administered together for increased efficacy. The overall goal of anti-angiogenic therapy is to reduce toxicity, reduce the risk of drug resistance and to increase anti-cancer efficacy.

摘要

越来越多的实验证据表明,肿瘤的生长和致死性依赖于血管生成。当通过给予特异性抑制血管内皮细胞生长的分子来抑制血管生成时,动物体内的肿瘤可被限制在休眠的微小尺寸,基本上无害。血管内皮细胞对肿瘤细胞发挥强大生长控制作用的最新证据来自以下研究:i. 在肿瘤床给予针对增殖血管内皮细胞的血管生成抑制剂;ii. 优化针对血管内皮细胞的传统细胞毒性化疗的剂量和疗程;iii. 将低剂量细胞毒性化疗仅靶向肿瘤床的血管内皮细胞;或iv. 通过联合给予血管生成抑制剂使肿瘤床的血管内皮细胞对放疗敏感。未来,抗血管生成疗法可能会被添加到传统化疗、放疗、免疫疗法或其他新型疗法如基因疗法中。此外,血管生成抑制剂可联合使用以提高疗效。抗血管生成疗法的总体目标是降低毒性、降低耐药风险并提高抗癌疗效。

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