Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs.

Angiogenesis is essential for tumour growth, invasion, and metastasis. Tumour blood vessels show many differences from normal vessels and are not genetically unstable, so they form a potentially key area for therapy of all types of cancer including leukaemias. Here we review current knowledge on the multiple pathways controlling tumour angiogenesis and assess which are the most clinically relevant. We also review the clinical evidence that angiogenesis affects the behaviour of cancer. Retrospective studies on intratumoral vascularisation suggest that it is an independent prognostic factor that merits prospective validation. Also, the presence of vascular endothelial growth factor in high concentrations in primary cancers is associated with poor prognosis. Key targets for drug development, current clinical trials, and the problems of developing drugs that do not have direct cytotoxic effects are reviewed. Recommendations are made on organising and monitoring antiangiogenic trials.