We are examining the effect that different doses of angiogenesis inhibitors exert on blood vessels and the relevance of these effects for anti-angiogenic therapy.

We have recently shown that angiogenesis inhibitors can exert very different effects on angiogenesis dependent on the concentration of drug that is present. We showed that although RGD-mimetic integrin inhibitors can inhibit angiogenesis at high doses, they potently promote VEGF-mediated angiogenesis and tumour growth at low concentrations (Reynolds et al., 2009). We are examining the dose-response characteristics of different inhibitors within in vitro angiogenesis models and using a number of biochemical approaches to identify mechanisms that allow different concentrations of angiogenesis inhibitors to exert different effects on angiogenesis. Successful therapy of cancer with anti-angiogenic agents is dependent on treatment of patients with the correct dosage. Our studies aim to elucidate appropriate dosing regimes for anti-angiogenic agents.