文章：

靶向恶性肿瘤中的ANGPT-TIE2通路

Targeting the ANGPT–TIE2 pathway in malignancy

原文发布日期：2010-08-01

DOI: 10.1038/nrc2894

类型: Review Article

开放获取: 否

要点：

1. The angiopoietin (ANGPT)–TIE system is crucial for the angiogenic switch in tumours, and together with vascular endothelial growth factor A (VEGFA) promotes the initiation of angiogenesis and maturation of new vessels. The ANGPT–TIE system is also involved in inflammation, metastasis and lymphangiogenesis.
2. ANGPT1 is a TIE2 agonist, and ANGPT2 functions as an antagonist or a partial agonist of TIE2 in different contexts. Both ANGPT1 and ANGPT2 have been shown to promote or inhibit tumorigenesis in various settings.
3. Agents specifically targeting ANGPT1 and ANGPT2 are currently in Phase II clinical trials and early reports suggest a promising anti-tumour activity and a safety profile distinct from those of anti-VEGFA agents.
4. Substantial combination benefit of targeting both the ANGPT2 and VEGFA pathways has been demonstrated preclinically.

要点翻译：

1. 血管生成素（ANGPT）-TIE系统对肿瘤中的血管生成开关至关重要，它与血管内皮生长因子A（VEGFA）共同促进新生血管的形成启动与成熟。该ANGPT-TIE系统还参与炎症、转移和淋巴管生成过程。
2. ANGPT1是TIE2激动剂，而ANGPT2在不同情境下可作为TIE2拮抗剂或部分激动剂。研究显示ANGPT1和ANGPT2在多种环境中均可能促进或抑制肿瘤发生。
3. 针对ANGPT1和ANGPT2的特异性靶向药物目前已进入II期临床试验阶段，早期报告表明其具有显著抗肿瘤活性，且安全性特征不同于抗VEGFA药物。
4. 临床前研究已证实，同时靶向ANGPT2与VEGFA通路可产生显著的联合治疗效益。

英文摘要：

Angiopoietins (ANGPTs) are ligands of the endothelial cell receptor TIE2 and have crucial roles in the tumour angiogenic switch. Increased expression of ANGPT2 relative to ANGPT1 in tumours correlates with poor prognosis. The biological effects of the ANGPT–TIE system are context dependent, which brings into question what the best strategy is to target this pathway. This Review presents an encompassing picture of what we know about this important axis in tumour biology. The various options for therapeutic intervention are discussed to identify the best path forwards.

摘要翻译： 

血管生成素（ANGPTs）是内皮细胞受体TIE2的配体，在肿瘤血管生成开关中发挥关键作用。肿瘤中ANGPT2相对于ANGPT1的表达增加与不良预后相关。ANGPT-TIE系统的生物学效应具有情境依赖性，这引发了针对该通路的最佳策略为何的疑问。本综述全面呈现了我们在肿瘤生物学中关于这一重要轴心的现有认知。文中探讨了多种治疗干预方案，以明确最佳的前进路径。

原文链接：

Targeting the ANGPT–TIE2 pathway in malignancy