Cediranib -: VEGFR inhibitor, antiangiogenic agent, oncolytic

Angiogenesis is a complex biological event in which vascular endothelial growth factor (VEGF) is considered the rate-limiting step. VEGF mediates both physiological and pathological angiogenesis via binding to specific transmembrane receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR or Flk-1), expressed mainly on vascular endothelial cells. Because angiogenesis in healthy adults is generally absent, interruption of VEGF signaling is an attractive strategy to selectively inhibit angiogenesis in solid tumors. Antagonism of VEGFR-2 has attracted particular attention due to the generally limited expression of this receptor in endothelium and the crucial role it plays in VEGF-mediated angiogenic signaling. Cediranib (AZD-2171, Recentin (TM)) is a novel, orally available quinazoline VEGFR inhibitor that was shown to potently inhibit VEGFR-1, VEGFR-2 and VEGFR-3 tyrosine kinase activity and VEGF-mediated signaling in vitro and in vivo. Cediranib exerted marked anticancer effects in vivo in a variety of xenograft models and in patients with advanced solid tumors. It continues to undergo clinical testing alone and in combination with selected chemotherapies for the oral treatment of various cancers.