Mechanisms and therapeutic implications of angiogenesis.

Angiogenesis is a key step in tumor growth and metastasis. Many angiogenic factors have been described, including vascular endothelial growth factor, basic fibroblast growth factor, and thymidine phosphorylase. More recently, a number of naturally occurring inhibitors of angiogenesis, including thrombospondin and angiostatin, have also been identified. The control of angiogenesis by inhibitors regulated by suppressor oncogenes or produced by tumors has emerged as an important mechanism. The development of quantitative assessment of vascular density in primary human tumors has produced a new independent marker of prognosis and could be helpful in selecting patients for antiangiogenic therapy. A large number of antiangiogenic agents are in development, however, new ways to assess their antitumor effects will be necessary for the treatment of advanced cancer. Stabilization of disease may occur by inhibiting new vessel growth, and thus, evidence for a decrease in blood supply should be sought by positron emission tomography scanning, magnetic resonance imaging, or other methods. Markers of angiogenesis in urine or blood will prove to be helpful in the monitoring of treatments.