ABSTRACT
Angiogenesis represents a complex mechanism of finely regulated mediators that act to promote new blood vessel growth and migration. This physiologic process is typically active only under specific circumstances where new blood vessels are recruited to aid in wound healing, promote overall growth of an organism (e.g., developing embryo), or in unique events, such as female menstruation (1). In 1971, Folkman (2) described the association between angiogenesis and the malignant potential of solid neoplasms, and proposed that without neovascularization, tumors would reach a maximum diameter of 2 to 3 mm (the maximum distance for the adequate diffusion of oxygen), and then enter a dormant state. He went on to hypothesize that by releasing a soluble chemical signal, tumors could effectively “activate” new blood vessel formation and growth, providing the necessary supply of oxygen and nutrients for continued growth and malignant transformation. By attempting to block this “tumor-angiogenesis factor” he hoped to one day be able to arrest neoplastic growth in this early stage, providing a powerful tool in the fight against cancer. In the 30 years since Folkman’s initial work, much has been elucidated about the regulation of angiogenesis and the potential targets within these pathways that might be exploited to halt malignant growth. Breast cancer research has recently seen a flood of work aimed at these very specific targets, many of which seem promising in a disease that continues to affect thousands of women every year. If Folkman’s predictions hold true, one means for arresting breast cancer in its early stages and preventing its malignant course may lie in the elegant controls of angiogenesis.
