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抗血管生成药物:现状与未来展望。

Anti-Angiogenics: Current Situation and Future Perspectives.

出版信息

Oncol Res Treat. 2018;41(4):166-171. doi: 10.1159/000488087. Epub 2018 Mar 23.

Abstract

Angiogenesis, the process leading to the formation of new blood vessels, is one of the hallmarks of cancer. Extensive studies established that i) vascular endothelial growth factor (VEGF) is a key driver of sprouting angiogenesis, ii) VEGF is overexpressed in most solid cancers, and iii) inhibition of VEGF can suppress tumor growth in animal models. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve the tumor of nutrients and oxygen, primarily through the blockade of VEGF/VEGF receptor signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, either alone or in combination with chemotherapy and other targeted therapies. However, inhibition of VEGF signaling is not effective in all cancers, and anti-angiogenics have often only limited impact on overall survival of cancer patients. This review focuses on the current status of FDA-approved anti-angiogenic antibodies and tyrosine kinase inhibitors and summarizes the progress and future directions of VEGF-targeted therapy.

摘要

血管生成,即导致新血管形成的过程,是癌症的特征之一。大量研究确立了以下观点:i)血管内皮生长因子(VEGF)是血管生成发芽的关键驱动因素,ii)VEGF 在大多数实体瘤中过度表达,以及 iii)抑制 VEGF 可以在动物模型中抑制肿瘤生长。这导致了抗血管生成的药理学制剂的开发,以破坏血管供应并使肿瘤缺氧和缺乏营养,主要通过阻断 VEGF/VEGF 受体信号传导。这一努力促成了 11 种抗 VEGF 药物被批准用于某些晚期癌症,单独使用或与化疗和其他靶向治疗联合使用。然而,VEGF 信号抑制在所有癌症中都不是有效的,抗血管生成药物通常对癌症患者的总生存期只有有限的影响。本综述重点介绍了 FDA 批准的抗血管生成抗体和酪氨酸激酶抑制剂的现状,并总结了 VEGF 靶向治疗的进展和未来方向。

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