Breast cancer angiogenesis: Prognostic factor and therapy target

Angiogenesis is essential for the growth and metastasis of rumours. In human breast cancer, quantitative assessment of vascular density (VD) in primary rumours has shown that high VD is associated with mctasrases and poor prognosis. In many studies high VD is the major independent predictor of poor prognosis and high VD is associated with poor survival even with adjuvant endocrine therapy or chemotherapy. The mechanisms involved in angiogenesis include the upregulation of vascular endothelial cell growth factor (VEGF) and also thymidine phosphorylase (TP). The latter metabolyses thymidine to 2-deoxyribose 1-phosphate which induces endothelial migration. We have shown that the proliferation rate of endothelial cells in human breast rumours is approximately fifty times greater than in normal breast. Other mechanisms involve macrophages which are significantly associated with high vascular density and poor outcome, Thus, the vasculature provides many novel targets for therapy, including drugs activated by angiogenic factors (capcetabine), antiproteases, inhibitors of VEGF signalling and gene therapy targeted to proliferating vessels. These approaches are likely to be most successful when applied to the earliest clinical stages and may be combined with drugs specifically toxic to hypoxic cells as part of a combined therapeutic strategy.