Vascular contribution to metastasis

It has been 40 years since Folkman's seminal paper [Cancer Res 1974. 34:2109-13], proposing the presence of a tumour associated angiogenic factor, which could be targeted as an anticancer therapy. There are currently a handful of drugs in trial or use that have been marketed as targeting angiogenesis. Unfortunately, the most widely used of these, bevacizumab (Avastin™, Roche), has met with limited success clinically. For this reason and based on a calculation of cost benefit, bevacizumab is now only publically subsidised for use in a limited range of solid tumours. That the contribution of vasculature to malignancy remains poorly understood is increasingly clear. At the same time, the traditional view that vascularisation is a passive participant in the process of malignancy, and that endothelium merely provides a conduit by which tumour cells spread, is being replaced with an understanding that vasculature is a key player in the process of metastasis. Furthermore, the identification of non-traditional sources of vasculature has complicated our understanding of the tumour endothelium as a unique population that can be simply targeted as an anticancer therapy. The following review seeks to provide an up-to-date view of vascular contribution to metastasis and implications for new vasculature-targeted anticancer treatments.