The Use of Artemisinin Compounds as Angiogenesis Inhibitors to Treat Cancer

Angiogenesis takes place during development, and vascular remodeling is a controlled ser‐ ies of events leading to neovascularization, which supports changing tissue requirements. Blood vessels and stromal components are responsive to proand anti-angiogenic factors that allow vascular remodeling during development, wound healing and pregnancy. In pathological situations such as cancer, however, the same angiogenic signaling pathways are induced and exploited. Cancer angiogenesis is a requirement for the development and growth of solid tumors beyond 2–3 mm3 (Cao et al., 2011). Several angiogenic activators in‐ cluding members of the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) gene families and various inhibitors of angiogenesis have been described. In steady-state conditions, the balance between angiogenic activators and inhibitors results in very limited new blood vessel growth in the majority of tissues. The balance tilts in favor of the angiogenic stimulators, however, in a variety of proliferative processes. It is now gener‐ ally accepted that angiogenesis is a rate-limiting process in tumor growth. Without new blood vessels to supply nutrients and dispose of catabolic products, tumor cells cannot sus‐ tain proliferation and thus are likely to remain dormant (Ferrara, 2010; Daniele et al., 2012).