Angiogenesis research: from laboratory to clinic

Abstract

Accumulating experimental evidence demonstrates that tumour growth and lethality are dependent on angiogenesis. When angiogenesis is inhibited by administering molecules which specifically suppress the growth of vascular endothelial cells, tumours in animals can be limited to a dormant microscopic size where they are essentially harmless. The most recent evidence that vascular endothelial cells exert potent growth control over tumour cells comes from the following studies, i. administration of an angiogenesis inhibitor specific for proliferating vascular endothelium in the tumour bed; ii. optimisation of the dose and schedule of conventional cytotoxic chemotherapy for the vascular endothelium; iii. targeting of low dose cytotoxic chemotherapy only to the vascular endothelium in the tumour bed; or iv. sensitisation of vascular endothelium in the tumour bed to radiotherapy by co-administration of an angiogenesis inhibitor. In the future, anti-angiogenic therapy may be added to conventional chemotherapy, radiotherapy, immunotherapy or other novel modalities such as gene therapy. Also, angiogenesis inhibitors may be administered together for increased efficacy. The overall goal of anti-angiogenic therapy is to reduce toxicity, reduce the risk of drug resistance and to increase anti-cancer efficacy.