Therapeutic options to target angiogenesis in human malignancies

Abstract

The critical role of angiogenesis in tumour growth and metastasis is now well established in the literature. Growing tumours stimulate neovascularisation through the secretion of pro-angiogenic growth factors, in particular, basic fibroblast growth factor and VEGF. Several lines of evidence have implicated VEGF in tumourigenesis, and understanding the role of VEGF in tumour angiogenesis has facilitated the development of novel targeting agents that specifically interfere with angiogenesis. Different approaches to disrupting tumour-induced angiogenesis encompass tyrosine kinase inhibitor, monoclonal antibodies, small-molecule inhibitors and transcription inhibitors. However, monoclonal antibody and tyrosine kinase inhibitors are the most advanced drug classes currently being investigated in clinical trials. So far, three anti-VEGF inhibitors, bevacizumab, sunitinib and sorafenib, have been approved for the treatment of solid human malignancies including colorectal cancer, gastrointestinal stromal tumours and renal cell carcinoma. Other antiangiogenic drugs are being investigated in various types of cancer. This review summarises the current literature on the use of these agents to interfere with VEGF, VEGF receptor, the matrix breakdown or other mechanisms involved in angiogenesis.

Keywords::

• angiogenesis
• antiangiogenesis inhibitor
• targeted therapy
• VEGF

Acknowledgement

The author thanks Amgen for funding IntraMed, New York, for editorial support in the preparation and styling of this manuscript.