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REVIEW: Tumor Angiogenesis Inhibitors

S. M. Kiselev*, S. V. Lutsenko, S. E. Severin, and E. S. Severin

Moscow Research Institute of Medical Ecology, Simferopolsky Bulvar 8, Moscow 117638, Russia; fax: (095) 113-4818; E-mail: sm_kiselev@mail.ru

* To whom correspondence should be addressed.

Received July 18, 2002
Formation of the blood supply system is a critical step in malignant transformation of neoplasms which results in the penetration of tumor cells into neighboring tissues and metastatic growth. Significant progress in the elucidation of mechanisms underlying tumor angiogenesis and the discovery of a great diversity of biomolecules involved in its regulation have culminated in the development of a radically new approach to antitumor therapy based on the search for efficient inhibitors of tumor angiogenesis. This review is devoted to the analysis of action mechanisms and expression of the major endogenous inhibitors involved in regulation of tumor and physiological angiogenesis. The antiangiogenic effects of the majority of currently known synthetic inhibitors are considered in the context of their roles in the main steps of tumor angiogenesis. Possible applications of antiangiogenic therapy in the chemotherapy of cancer diseases are discussed.
KEY WORDS: tumor angiogenesis inhibitors, angiogenic growth factors, endothelial cell proliferation, endothelial cell migration, proteolytic enzymes, extracellular matrix, cell adhesion molecules