Therapeutic targets of multiple angiogenic factors for the treatment of cancer and metastasis.

Like any growing healthy tissues, tumors build up their blood vessels by three mechanisms: angiogenesis, vasculogenesis, and intersucception. Vascular endothelial growth factor-A (VEGF-A) is one of the key factors responsible for stimulation and maintenance of the disorganized, leaky, and torturous tumor vasculature. In addition to VEGF-A, tumors produce multiple other factors to stimulate blood vessel growth. These include members in the platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), VEGF-C, insulin-like growth factor (IGF), angiopoietin (Ang), and hepatocyte growth factor (HGF) families. Recent studies show that these angiogenic factors can also promote lymphangiogenesis and potentially lymphatic metastasis. Understanding the roles of individual and combined angiogenic factors in promoting tumor angiogenesis is crucial for defining therapeutic targets and antiangiogenic drug development for the treatment of cancer.