Chapter 7 - Tumor vasculature as a target

Abstract

The chapter focuses on the utility of various vascular targeting approaches and antiangiogenesis strategies in the treatment of cancer. Angiogenesis, the formation of new blood vessels from pre-existing ones, is thought to be obligatory for tumor growth and the formation of metastasis. The angiogenic switch, which is the change from an avascular tumor to an abundantly vascularized tumor, is coordinated by both positive and negative regulators. The migration and proliferation of the endothelial cells, and remodeling of the extracellular matrix are both essential events in angiogenesis. During the last three decades, effort has been made to further identify and characterize all the proteins that have an important role in angiogenesis. Groups of proteins that are known to have a role in angiogenesis are the angiogenic factors, the integrins, the plasminogen activation system, and the matrix metalloproteinases, and their inhibitors. The function, interaction, regulation, and clinical relevance of these proteins and their receptors have been extensively investigated, and strategies interfering with different stages in the process of angiogenesis have been designed to inhibit tumor growth. Several biological and chemical compounds that interfere with the process of angiogenesis were also developed. Furthermore, in the last decade, endogenous inhibitors of angiogenesis, and peptides or antibodies that target the tumor's vasculature have also been identified and characterized. Targeting or homing of antibodies or peptides toward the tumor vasculature is one of the new promising anticancer strategies. However, the main challenge in this strategy is to find surface markers on angiogenic endothelial cells that do not show cross-reactivity with resting endothelial cells.