Tumor angiogenesis and anti-angiogenic therapy

Keio J Med. 2012;61(2):47-56. doi: 10.2302/kjm.61.47.


Anti-angiogenic therapy is an anti-cancer strategy that targets the new vessels that grow to provide oxygen and nutrients to actively proliferating tumor cells. Most of the current anti-cancer reagents used in the clinical setting indiscriminately target all rapidly dividing cells, resulting in severe adverse effects such as immunosuppression, intestinal problems and hair loss. In comparison, anti-angiogenic reagents theoretically have fewer side effects because, except in the uterine endometrium, neoangiogenesis rarely occurs in healthy adults. Currently, the most established approach for limiting tumor angiogenesis is blockade of the vascular endothelial growth factor (VEGF) pathway. In line with the results of preclinical studies, significant therapeutic effects of VEGF blockers have been reported in various types of human cancers, even in patients with progressive/recurrent cancer who could not otherwise be treated. However, some patients are refractory to this treatment or acquire resistance to VEGF inhibitors. Moreover, several studies have shown that VEGF blockade damages healthy vessels and results in adverse effects such as hemorrhagic and thrombotic events. In recent research that indicated possible ways to overcome these problems, several VEGF-independent and tumor-selective pro-angiogenic mechanisms were discovered that could be targeted in combination with or without conventional VEGF blockade. These findings offer opportunities to greatly improve current anti-angiogenic treatment for cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Angiopoietins / antagonists & inhibitors
  • Angiopoietins / metabolism
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Drug Resistance, Neoplasm / drug effects
  • Fibroblast Growth Factors / antagonists & inhibitors
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Macrophage Colony-Stimulating Factor / antagonists & inhibitors
  • Macrophage Colony-Stimulating Factor / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases / metabolism
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / prevention & control*
  • Placenta Growth Factor
  • Pregnancy Proteins / antagonists & inhibitors
  • Pregnancy Proteins / metabolism
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors


  • Angiogenesis Inhibitors
  • Angiopoietins
  • Antineoplastic Agents
  • Cytokines
  • Matrix Metalloproteinase Inhibitors
  • PGF protein, human
  • Pregnancy Proteins
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor
  • Fibroblast Growth Factors
  • Macrophage Colony-Stimulating Factor
  • Matrix Metalloproteinases