Novel Drugs with High Efficacy against Tumor Angiogenesis

Int J Mol Sci. 2022 Jun 22;23(13):6934. doi: 10.3390/ijms23136934.

Abstract

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.

Keywords: HSP inhibitors; Tie/Ang; VEGF/VEGFR; anti-tumor angiogenesis; novel drugs.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Angiopoietins
  • Antineoplastic Agents* / pharmacology
  • HSP90 Heat-Shock Proteins
  • Humans
  • Hypoxia / drug therapy
  • Neoplasms* / drug therapy
  • Neoplasms* / pathology
  • Neovascularization, Pathologic / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factors

Substances

  • Angiogenesis Inhibitors
  • Angiopoietins
  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Grants and funding

This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CAMS-I2M, 2021-I2M-1-072), National Natural Science Foundation of China (32072722, 32072721), and National Transgenic Creature Breeding Grand Project (2016zx08008-003).