Challenges facing antiangiogenic therapy for cancer: impact of the tumor extracellular environment.

It is well known that angiogenesis plays an important role in malignant tumor progression. Thus, a great deal of effort has been focused on the development and evaluation of novel angiogenesis inhibitors for the treatment of human malignancies. In this review, the role of angiogenesis in tumor growth will be examined, as well as efforts to develop and use antiangiogenic therapies to treat malignant tumors. In particular, focus will be on the extracellular environment and the challenges of using antiangiogenic therapy in the clinical setting, in terms of toxicities, potential mechanisms of tumor resistance and optimization of clinical trial design. Attention will be focused upon a mechanistic understanding of the variability and dynamic nature of individual tumor microenvironments, and the potential impact this has on antiangiogenic therapies. Copyright Future Drugs Ltd.