Antiangiogenic therapy for cancer: an update

Abstract

The idea of antiangiogenic therapy was the brainchild of Dr. Judah Folkman in the early 1970s. He proposed that by cutting off the blood supply, cancer cells would be deprived of nutrients and, hence, treated. His efforts paid off when bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, was approved as antiangiogenic therapy in 2004 for the treatment of colon cancer. Since then, an array of antiangiogenic inhibitors, either as monotherapy or in combination with other cytotoxic and chemotherapy drugs, have been developed, used in clinical trials, and approved for the treatment of cancer. Despite this important breakthrough, antiangiogenic therapy for cancer met with a number of hurdles on its way to becoming an option for cancer therapy. In this article, we summarize the most current information on the mechanisms of tumor angiogenesis, proangiogenic and antiangiogenic factors, potential targets and their mechanisms of action, and experimental evidences, as well as the most recent clinical trial data on antiangiogenic agents for cancer therapy.

Figure 1. Main events in Angiogenesis

Tumors cells, exposed to hypoxia within the tumor core, induce the expression of many factors that in turn recruit endothelial cells to the core of the tumor and promote the formation of new blood vessels. Interactions of both cell types result in many events and leads to the recruitment of many other cell lines. This recruitment of other cell lines completes a vicious cycle that further stabilizes the newly formed blood vessels and enhances tumor growth and angiogenesis.