College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
National Health Commission (NHC) of China Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China.
Int J Mol Sci. 2022 Jun 22;23(13):6934. doi: 10.3390/ijms23136934.
Angiogenesis is involved in physiological and pathological processes in the body. Tumor angiogenesis is a key factor associated with tumor growth, progression, and metastasis. Therefore, there is great interest in developing antiangiogenic strategies. Hypoxia is the basic initiating factor of tumor angiogenesis, which leads to the increase of vascular endothelial growth factor (VEGF), angiopoietin (Ang), hypoxia-inducible factor (HIF-1), etc. in hypoxic cells. The pathways of VEGF and Ang are considered to be critical steps in tumor angiogenesis. A number of antiangiogenic drugs targeting VEGF/VEGFR (VEGF receptor) or ANG/Tie2, or both, are currently being used for cancer treatment, or are still in various stages of clinical development or preclinical evaluation. This article aims to review the mechanisms of angiogenesis and tumor angiogenesis and to focus on new drugs and strategies for the treatment of antiangiogenesis. However, antitumor angiogenic drugs alone may not be sufficient to eradicate tumors. The molecular chaperone heat shock protein 90 (HSP90) is considered a promising molecular target. The VEGFR system and its downstream signaling molecules depend on the function of HSP90. This article also briefly introduces the role of HSP90 in angiogenesis and some HSP90 inhibitors.
血管生成参与体内的生理和病理过程。肿瘤血管生成是与肿瘤生长、进展和转移相关的关键因素。因此，开发抗血管生成策略具有重要意义。缺氧是肿瘤血管生成的基本起始因素，导致缺氧细胞中血管内皮生长因子（VEGF）、血管生成素（Ang）、缺氧诱导因子（HIF-1）等的增加。VEGF 和 Ang 通路被认为是肿瘤血管生成的关键步骤。目前有许多针对 VEGF/VEGFR（VEGF 受体）或 ANG/Tie2，或两者的抗血管生成药物用于癌症治疗，或仍处于临床开发或临床前评估的各个阶段。本文旨在综述血管生成和肿瘤血管生成的机制，并重点介绍抗血管生成治疗的新药和新策略。然而，单独使用抗肿瘤血管生成药物可能不足以根除肿瘤。分子伴侣热休克蛋白 90（HSP90）被认为是一个很有前途的分子靶点。VEGFR 系统及其下游信号分子依赖于 HSP90 的功能。本文还简要介绍了 HSP90 在血管生成中的作用以及一些 HSP90 抑制剂。
