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首页> 外文期刊>Endothelium: Journal of endothelial cell research >Vascular integrins in tumor angiogenesis: mediators and therapeutic targets.
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Vascular integrins in tumor angiogenesis: mediators and therapeutic targets.

机译:肿瘤血管生成中的血管整合素:介质和治疗靶标。

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摘要

The notion that tumor angiogenesis may have therapeutic implications in the control of tumor growth was introduced by Dr. Judah Folkman in 1971. The approval of Avastin in 2004 as the first antiangiogenic systemic drug to treat cancer patients came as a validation of this visionary concept and opened new perspectives to the treatment of cancer. In addition, this success boosted the field to the quest for new therapeutic targets and antiangiogenic drugs. Preclinical and clinical evidence indicate that vascular integrins may be valid therapeutic targets. In preclinical studies, pharmacological inhibition of integrin function efficiently suppressed angiogenesis and inhibited tumor progression. alphaVbeta3 and alphaVbeta5 were the first vascular integrins targeted to suppress tumor angiogenesis. Subsequent experiments revealed that at least four additional integrins (i.e., alpha1beta1, alpha2beta1, alpha5beta1, and alpha6beta4) might be potential therapeutic targets. In clinical studies low-molecular-weight integrin inhibitors and anti-integrin function-blocking antibodies demonstrated low toxicity and good tolerability and are now being tested in combination with radiotherapy and chemotherapy for anticancer activity in patients. In this article the authors review the role of integrins in angiogenesis, present recent development in the use of alphaVbeta3 and alpha5beta1 integrin antagonists as potential therapeutics in cancer, and discuss future perspectives.
机译:Judah Folkman博士于1971年提出了肿瘤血管生成可能对肿瘤生长的控制具有治疗意义的观念。2004年,Avastin作为第一种抗血管生成的全身性药物用于治疗癌症患者的批准,证明了这一远见的构想和开启了癌症治疗的新视野。此外,这一成功推动了该领域对新治疗靶标和抗血管生成药物的追求。临床前和临床证据表明,血管整合素可能是有效的治疗靶标。在临床前研究中,对整联蛋白功能的药理抑制作用可有效抑制血管生成并抑制肿瘤进展。 alphaVbeta3和alphaVbeta5是第一个靶向抑制肿瘤血管生成的血管整合素。随后的实验表明,至少有四个额外的整合素(即alpha1beta1,alpha2beta1,alpha5beta1和alpha6beta4)可能是潜在的治疗靶标。在临床研究中,低分子量整联蛋白抑制剂和抗整联蛋白功能阻断抗体显示出低毒性和良好的耐受性,目前正在与放疗和化学疗法联合测试患者的抗癌活性。在本文中,作者回顾了整联蛋白在血管生成中的作用,介绍了将αVbeta3和alpha5beta1整联蛋白拮抗剂用作癌症潜在治疗剂的最新进展,并讨论了未来的观点。

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