From antiangiogenesis to hypoxia: current research and future directions.

Angiogenesis has long been recognized as an essential element in tumor growth. Since the conception of antiangiogenesis for cancer therapeutics, great strides have been made in understanding the molecular biology underlying angiogenesis, both in cancer and in physiology. By capitalizing on these advancements through bench-to-bedside research, potent antiangiogenic agents have been developed and tested. To date, the clinical results of most of these antiangiogenic agents have not met expectations. Even with the most successful agents, such as bevacizumab, used either as single agents or in combination with chemotherapy, gains in overall survival of cancer patients have been modest in most cases. In this article, the authors present the evolving views of antiangiogenic therapy, review recent experimental and clinical studies on antiangiogenesis, and address the fundamental role of hypoxia in tumor progression, which may be key to improving the efficacy of antiangiogenic therapy.