Angiogenesis and melanoma - from basic science to clinical trials.

The effective management of malignant melanoma has remained centred around the surgeon. The arrival of anti-angiogenic agents as the 'fourth' cancer treatment joining the ranks of surgery, chemotherapy and radiotherapy has been a source of renewed hope. This article provides an up-to-date review of the focus, state and rationale of clinical trials of anti-angiogenic therapies in metastatic malignant melanoma. Vascular Endothelial Growth Factor (VEGF) is by no means the only target, although perhaps the most extensively studied following the successful introduction of the anti-VEGF Antibody bevacizumab. This has been combined with other established therapies to try and improve outcomes in metastatic disease, and is being trialled in the UK to prevent metastasis in high-risk patients. We describe the encouraging preclinical work that lead to great enthusiasm for these agents, assess the key trials and their outcomes, discuss why these therapies have not revolutionised melanoma care and explore how they might be better targeted in the future.