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抗血管生成疗法。

Antiangiogenic therapy.

作者信息

Albo Daniel, Wang Thomas N, Tuszynski George P

机构信息

Department of Surgery, Section of Surgical Oncology, Medical College of Georgia, Augusta, GA 30912, USA.

出版信息

Curr Pharm Des. 2004;10(1):27-37. doi: 10.2174/1381612043453522.

Abstract

Angiogenesis, the formation of blood vessels from preexisting ones, plays a crucial role in tumor progression. Activation of an "angiogenic switch" allows tumor cells to invade and metastasize. The growing interest in the use of antiangiogenic agents in the treatment and prevention of cancer lies in the theoretical advantages of this molecularly targeted modality of chemotherapy. Delivery of antiangiogenic agents are not complicated by having to penetrate large bulky masses but, instead, have easy access to tumoral endothelial cells. Antiangiogenic drugs may not cause cytopenias and thus will avoid many of the unwarranted toxicities of standard chemotherapeutic agents. Because they act directly on nascent endothelial cells, antiangiogenic agents may avoid tumor resistance mechanisms. If antiangiogenic agents are successful, they might be applicable to many tumor types and not be dependent on cell type or growth fraction of cells within a tumor. However, several important obstacles remain with regards to using antiangiogenic drugs in clinical trials with which we must contend in order to determine accurately the efficacy of these agents. In this article, we review the different classes of antiangiogenic agents available, ongoing clinical trials, as well as potential pitfalls and future directions in this exciting field.

摘要

血管生成,即从已有的血管形成新的血管,在肿瘤进展中起着关键作用。“血管生成开关”的激活使肿瘤细胞能够侵袭和转移。在癌症治疗和预防中使用抗血管生成药物的兴趣日益浓厚,这源于这种分子靶向化疗方式的理论优势。抗血管生成药物的递送不会因需要穿透大块肿瘤而变得复杂,相反,它们很容易作用于肿瘤内皮细胞。抗血管生成药物可能不会导致血细胞减少,因此可以避免许多标准化疗药物不必要的毒性。由于它们直接作用于新生内皮细胞,抗血管生成药物可能避免肿瘤耐药机制。如果抗血管生成药物取得成功,它们可能适用于多种肿瘤类型,而不依赖于肿瘤内细胞的类型或生长分数。然而,在临床试验中使用抗血管生成药物仍存在几个重要障碍,我们必须应对这些障碍,以便准确确定这些药物的疗效。在本文中,我们回顾了现有的不同类别的抗血管生成药物、正在进行的临床试验,以及这个令人兴奋的领域中的潜在陷阱和未来方向。

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