Role of angiogenesis in the pathogenesis of cancer.

It has been recognized for decades that angiogenesis is an important event in tumor growth and metastasis; the concept of the “angiogenic switch,” whereby tumors acquire the ability to grow exponentially and disseminate beyond their primary site, is one of the central components in our understanding of cancer. A vast network of signaling molecules and receptors that are involved in the regulation of angiogenesis have been identified and characterized; most notably, the vascular endothelial growth factor (VEGF) family. Indeed, the VEGF family of growth factors and receptors has become a prototype for our understanding of angiogenesis during early development and in pathological conditions such as cancer. The specific inhibition of key regulatory molecules including VEGF-A (such as with bevacizumab treatment) has been recognized as a useful strategy to reduce tumor growth and progression in several tumor types. Nevertheless, the contribution of other members of the VEGF family, other signaling pathways, and also endogenous angiogenic inhibitors to tumor angiogenesis, is beginning to emerge. The diversity of pathways and molecules involved in the regulation of angiogenesis in both normal development and cancer will likely offer many more prospects for successful therapeutic intervention.