VEGF as a target of therapy in gastrointestinal oncology

The last decade has seen enormous progress in understanding the development of cancer. It is now recognized that tumor growth is a multistep process that may take years to become clinically relevant. Angiogenesis is an absolute requirement for tumors to become clinically detectable. The importance of angiogenesis for tumor growth is supported by several clinical studies that showed a positive correlation between tumor angiogenesis and tumor stage. In animal studies, inhibition of angiogenesis caused impressive reduction of tumor growth. The aim of antivascular therapy in the treatment of cancer is to attack the tumor through its vasculature. Antivascular therapy can be divided in two different areas: (1) inhibition of angiogenesis with the aim to prevent formation of new blood vessels and (2) vascular targeting agents with the goal to destroy the existing tumor vasculature. Vascular endothelial growth factor (VEGF) has been recognized as one of the most important factors involved in tumor angiogenesis and has become an important target for anticancer treatment. This review focuses mainly on the inhibition of angiogenesis in gastrointestinal tumors by blocking the VEGF receptor/ligand signaling. We will discuss the biology of the VEGF receptor/ligand signaling system and give an overview of the current approaches for therapy in gastrointestinal cancer targeting the VEGF signaling pathway.