文章：

VEGF靶向治疗：抗肿瘤活性的机制

VEGF-targeted therapy: mechanisms of anti-tumour activity

原文发布日期：2008-07-01

DOI: 10.1038/nrc2403

类型: Review Article

开放获取: 否

要点：

1. Vascular endothelial growth factor (VEGF) mediates numerous changes within the tumour vasculature, including endothelial cell proliferation, migration, invasion, survival, chemotaxis of bone marrow-derived progenitor cells, vascular permeability and vasodilation.
2. There are several approaches to inhibiting VEGF signalling, including neutralization of the ligand or receptor by antibodies, and blocking VEGF receptor (VEGFR) activation and signalling with tyrosine kinase inhibitors.
3. VEGF-targeted therapy has been shown to be efficacious as a single agent in renal cell carcinoma and hepatocellular carcinoma, whereas it is only of benefit when combined with chemotherapy for patients with metastatic colorectal, non-small-cell lung and metastatic breast cancer.
4. VEGF-targeted therapy affects numerous cell types within the tumour microenvironment, including endothelial cells, haematopoietic progenitor cells, dendritic cells and tumour cells.
5. VEGF-targeted therapy has multiple mechanisms of action that might be dependent on tumour type.
6. VEGF-targeted therapy affects vascular function (flow and permeability) in addition to blocking further new blood vessel growth.

要点翻译：

1. 血管内皮生长因子（VEGF）介导肿瘤脉管系统的多种变化，包括内皮细胞增殖、迁移、侵袭、存活、骨髓来源祖细胞的趋化性、血管通透性和血管舒张。
2. 目前有几种抑制VEGF信号传导的方法，包括通过抗体中和配体或受体，以及使用酪氨酸激酶抑制剂阻断VEGF受体（VEGFR）的激活和信号传导。
3. 靶向VEGF治疗已被证明在肾细胞癌和肝细胞癌中作为单一疗法有效，而对于转移性结直肠癌、非小细胞肺癌和转移性乳腺癌患者，仅在与化疗联合使用时才有获益。
4. 靶向VEGF治疗影响肿瘤微环境中的多种细胞类型，包括内皮细胞、造血祖细胞、树突状细胞和肿瘤细胞。
5. 靶向VEGF治疗具有多种作用机制，这些机制可能因肿瘤类型而异。
6. 除阻断新生血管生长外，靶向VEGF治疗还会影响血管功能（血流和通透性）。

英文摘要：

Several vascular endothelial growth factor (VEGF)-targeted agents, administered either as single agents or in combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies. VEGF-targeted therapies were initially developed with the notion that they would inhibit new blood vessel growth and thus starve tumours of necessary oxygen and nutrients. It has become increasingly apparent, however, that the therapeutic benefit associated with VEGF-targeted therapy is complex, and probably involves multiple mechanisms. A better understanding of these mechanisms will lead to future advances in the use of these agents in the clinic.

摘要翻译： 

几种靶向血管内皮生长因子（VEGF）的药物，无论是单独使用还是与化疗联合使用，均已显示出对晚期恶性肿瘤患者具有益处。VEGF靶向治疗最初是基于其能够抑制新血管生成，从而“饿死”肿瘤所需的氧气和营养。然而，越来越多的证据表明，VEGF靶向治疗所带来的疗效机制复杂，可能涉及多种作用机制。更深入地理解这些机制，将有助于未来在临床上更好地应用这些药物。

原文链接：

VEGF-targeted therapy: mechanisms of anti-tumour activity