Angiogenesis is the growth of new blood vessels in the body. Abnormal angiogenesis is recognised as a “common denominator” in many disease processes, and the development of angiogenesis inhibitors holds great hope in the ongoing battle against cancer. The field of angiogenesis has roots in the Hunterian era of the late eighteenth century but did not begin to blossom until the early 1970s when the then controversial findings and conclusions of Judah Folkman, the “father of angiogenesis,” were first published. There were only 65 publications with angiogenesis in the title in the 10 years after Folkman first proposed the idea of tumour angiogenesis, compared to over 9,000 publications from the year 2000 to 2010. In this review we will explore the voyage of discovery from the first observations of John Hunter in the eighteenth century, via the struggle faced by Folkman to prove the importance of angiogenesis, and finally how his determination has led to modern angiogenesis inhibitors being used in everyday clinical practice. 1. Angiogenesis Angiogenesis is the formation of new blood vessels from preexisting vessels and is a normal and highly regulated physiological process throughout the body. Since physiological angiogenesis is associated only with tissue growth, tissue repair, and the reproductive cycle, angiogenesis in normal adult tissues is a very rare event, and the endothelium of most tissues is therefore an extremely stable population of cells with very low mitotic activity [1]. Angiogenesis also occurs after implantation of the blastocyst of the embryo to the uterus. This produces the placenta [2, 3] and was first observed in pregnant monkeys by Hertig in 1935 [4]. In the developing embryo both angiogenesis and the earlier distinct process of vasculogenesis are required for foetal growth and viability [5]. 2. The Beginnings of Angiogenesis: From Hunter to Folkman—A Slow Beginning The founder of “scientific surgery” John Hunter (1728–1793), who sought to provide an experimental basis to surgical practice, first used the term angiogenesis in 1787 [1]. He stated that vessels “would appear to have more powers of perfecting themselves, when injured, than any other part of the body; for their use is almost immediate and constant, and it is they which perform the operation of restoration on the other parts, therefore they themselves must first be perfect” [6]. He noted the early appearance of new blood vessels to supply the growing antlers from the Fallow Deer’s skull, observing “a soft membranous pulp shooting out from this knob which is extremely
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