Recent advances in angiogenesis drug development

Early cancer researchers investigating the conditions necessary for cancer metastasis observed that one of the critical events required for tumor growth is an increased vascularization and the formation of a new network of blood vessels called angiogenesis. Indeed it was nearly 70 years ago that the existence of tumor-derived factors responsible for promoting new vessel growth was postulated [1] and that tumor growth is essentially dependent on vascular induction and the development of a neovascular supply [2]. By the late 1960s, Dr. Judah Folkman and colleagues had begun the search for a tumor angiogenesis factor [3]. In his 1971 landmark report, Folkman proposed that inhibition of angiogenesis by means of holding tumors in a nonvascularized dormant state would be an effective strategy to treat human cancer, and hence laid the groundwork for the concept behind the development of antiangiogenic drugs [4]. This fostered the search for angiogenic factors, regulators of angiogenesis, and antiangiogenic molecules over the next three decades, shedding light on angiogenesis as an important therapeutic target for the treatment of cancer and other angiogenesis-dependent disease states. Successful development and clinical translation of antiangiogenic agents depends on the complete understanding of the biology of angiogenesis and the regulatory proteins that govern this angiogenic process, topics which have been covered in greater detail in another section of this book. This chapter will discuss the recent advances in the angiogenesis drug development arena, highlighting the FDA approved drugs and investigational agents in the preclinical and clinical stage of development.