Vandetanib, A Dual Inhibitor of VEGFR and EGFR Tyrosine Kinase Activity

Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, is fundamental to support tumor growth. Inhibiting tumor angiogenesis is a promising strategy for treatment of cancer and has been successfully transferred from preclinical to clinical application in recent years. Due to its role in tumor angiogenesis, the vascular endothelial growth factor (VEGF) and its receptor have been a major focus of basic research and drug development in the field of oncology. Vandetanib, is an orally bioavailable inhibitor of VEGF receptor-2 tyrosine kinase activity that in preclinical studies has been shown to inhibit both VEGF-induced signalling in endothelial cells and tumourinduced angiogenesis. Consistent with inhibition of angiogenesis, vandetanib, produced significant broad-spectrum antitumour activity in a panel of histologically diverse human tumour xenografts. In addition to its antiangiogenic properties, vandetanib also has activity against the epidermal growth factor receptor (EGFR) tyrosine kinase, which could impart a direct inhibitory effect on tumour cell growth and survival. Early clinical evaluation of this agent has demonstrated a safety profile and comprehensive series of phase II studies have clarify the value of this approach in the treatment of solid tumor. This review summarises preclinical and clinical studies with this unique agent.