ROLE OF ANGIOGENESIS IN TUMOR PROGRESSION Angiogenesis inhibitors therapy: From promising experimental animal models to reality of clinical use

Abstract

Summary. The development of new blood vessels (angiogenesis) is necessary to sustain the growth of primary tumor as well as a process of tumor metastasis. Cancer cells activate the quiescent vasculature to produce new blood vessels via an »angio- genic switch«. Understanding of molecular mechanisms involved in that process is essential for the development of antiangiogenic drugs. Drugs that inhibit angiogenesis could offer a treatment that is complementary to traditional chemotherapy. Chemotherapy directly targets tumor cells, which are prone to develop acquired drug resistance due to genetic instability. Antiangiogenic therapy is directed against endothelial cells in tumor stroma, which are genetically stabile. First results from animal studies supported the theory that endothelial cells do not develop drug resitance and had excellent results in inducing tumor quiescence. However, recent clinical trials showed that antiangiogenic therapy has limitations but that it can improve conventional thera- peutic modalities of disseminated disease.