Translating angiogenesis research into the clinic: the challenges ahead.

The field of angiogenesis research has evolved to become one of the most rapidly growing biomedical disciplines. The interest in basic angiogenesis research is sparked by the translational therapeutic potential aimed at developing anti-angiogenesis as a novel therapeutic modality for tumours and a number of non-oncological diseases, such as rheumatoid arthritis, psoriasis, diabetic retinopathy and age-dependent macula degeneration. The molecular determinants of the angiogenic cascade have been characterized in great detail over the last few years. Likewise, intense ongoing efforts are aimed at identifying and validating additional vascular specific determinants that may be exploited as therapeutic targets for pro-angiogenic and anti-angiogenic therapy. At the same time, a large number of angiomodulatory compounds are in various phases of clinical trials. These include the neutralizing vascular endothelial growth factor (VEGF) antibody Avastin, which has successfully passed phase III clinical trials for the combination with chemotherapy in colorectal cancers. In view of the dramatic progress in basic angiogenesis research, surprisingly little is known about the nature of the neovasculature in human tumours. The inclusion and exclusion criteria of clinical trials of anti-angiogenic compounds are devoid of angiogenesis-related parameters and reliable biomarkers to trace the efficacy of an anti-angiogenic intervention are largely missing. Based on a brief review of the biology of the angiogenic cascade, this review provides an overview of the current concepts of the angiogenic vasculature in human tumours and discusses some key unanswered questions in translating angiogenesis research into the clinic.