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The basic molecular biology of angiogenesis and its implication in anticancer therapeutics

Angiogenesis is a physiological process through which new blood vessels are formed from the existing blood vessels. It is a multistep process, involving proliferation of activated endothelial cells (ECs) and migration of ECs to target organs. At target organs, the ECs get organized into capillary tubes and synthesize new basement membrane. These capillary tubes then get canalized to form a vascular lumen. The process of Angiogenesis plays an important role in growth and progression of cancer. The control of tumor angiogenesis depends upon the net balance of angiogenic factors (activators) and antiangiogenic factors (inhibitors), which are secreted by both tumor cells and host cells. The key signaling angiogenic factors include vascular endothelial growth factor (VEGF), Notch, angiopoietin, ephrins, transforming growth factor beta, and platelet derived growth factors (PDGFs). The potential therapeutic implication of tumor angiogenesis was coined by Folkman in 1971. The knowledge of tumor angiogenesis can be utilized in the development of novel strategies of anticancer therapy by targeting tumor vessels instead of tumor cells. It works best when combined with cancer chemotherapy. However, there are many hurdles to the road of success. The long-term survival and overall improvement in advanced cancer are still limited, and the final outcome may be different from what is obtained in experimental animals. In this article, an effort is made to address the process of angiogenesis, the basic molecular biology of key signaling pathways and the concept, present status and challenges in cancer therapeutics as far as angiogenesis is concerned.