Blockade of neoangiogenesis, a new and promising technique to control the growth of malignant tumors and their metastases

Abstract

Neoangiogenesis, the development of new blood vessels from a pre-existing vasculature involves the migration behavior, proliferation and differentiation of endothelial cells. This process is an important aspect to both the growth and metastasis of solid tumors. In growing tumors, the development of a sufficient vascular supply is a highly complex event, which is controlled by many factors. An interaction between tumor cells, endothelial cells, macrophages, fibroblasts, and the extracellular matrix, all of which are capable of releasing factors influencing the angiogenic mechanisms is necessary for the building of new sufficient vascular structures. The increased understanding of the balance of angiogenesis and mechanisms of vascular control allowed the development of new therapeutic substances that influence that process in different ways. For example, work done over the last decade has elucidated the central role of vascular endothelial growth factor (VEGF) in the regulation of normal and pathological angiogenesis. Therefore, the blockade of VEGF signaling is currently a major part of strategies for the therapy of malignant tumors. Several studies tested neutralizing antibodies against mature VEGF protein or its isoforms, blockade of VEGF receptors by VEGF receptor antibodies, soluble VEGF receptor mutants or fusion-proteins and finally, intracellular interference with VEGF mRNA or signaling in the target cell. In this review, we present strategies and substances for the blockade of neoangiogenesis that are already in clinical use or in pre-clinical trials. Also the combination of these approaches with conventional chemotherapy or radiotherapy will be discussed.