Abstract
Angiogenesis is deeply involved in the progression of major diseases such as cancer, diabetes, and rheumatoid arthritis. Molecular mechanism on angiogenesis was extensively studied, and several signaling systems including VEGF (VEGF-A), angiopoietin, PDGF, and ephrin were shown to be crucial for physiological angiogenesis. Interestingly, among these factors, VEGF appears to play key roles in most of the pathological angiogenesis, and other factors are considered to have additional effects on its development depending on the situation. VEGF binds and activates two tyrosine kinase receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and stimulates endothelial cell growth, survival, and vascular permeability. VEGF induces not only tumor angiogenesis but also blood-vessel-dependent metastasis. Based on the importance of VEGF in diseases, many companies and institutes are now trying to generate appropriate small molecules as well as proteins that strongly antagonize the VEGF-VEGFR system. Several molecules quite effective for suppression of tumorigenesis and pathological angiogenesis in animal models are under clinical trials.
