Varner J A, Cheresh D A
Department of Immunology, Scripps Research Institute La Jolla, California, USA.
Important Adv Oncol. 1996:69-87.
Angiogenesis is a critical process for the growth and metastatic properties of all solid tumors. Recent biological and molecular studies have begun to elucidate the basic mechanisms of vascular cell proliferation, motility, and differentiation in vitro and in vivo. With this knowledge, it should be feasible to devise therapeutic strategies to selectively target and perturb the biological processes of angiogenic vascular cells, thereby leading to effective inhibitors of angiogenesis. This strategy has led to the development of antagonists to integrin alpha v beta 3, which promote the unscheduled programmed cell death of newly sprouting blood vessels. These antagonists cause regression of preestablished human tumors growing in laboratory animals and thus may lead to an effective therapeutic approach for most solid tumors in humans. Studies are currently aimed at designing highly specific small organic integrin inhibitors that will disrupt the signals enabling vascular cells to respond to the tumor-associated extracellular environment and to promote tumor-induced angiogenesis.
血管生成是所有实体瘤生长和转移特性的关键过程。最近的生物学和分子研究已开始阐明血管细胞在体外和体内增殖、运动及分化的基本机制。有了这些知识，设计治疗策略以选择性地靶向并干扰血管生成性血管细胞的生物学过程，从而开发出有效的血管生成抑制剂应该是可行的。这一策略已促成了整合素αvβ3拮抗剂的研发，该拮抗剂可促使新萌生血管发生意外的程序性细胞死亡。这些拮抗剂可使实验动物体内预先形成的人类肿瘤消退，因此可能为人类大多数实体瘤带来有效的治疗方法。目前的研究旨在设计高度特异性的有机小分子整合素抑制剂，这类抑制剂将破坏使血管细胞对肿瘤相关细胞外环境作出反应并促进肿瘤诱导血管生成的信号。
