Abstract 5094: Angiopoietin-2 antagonist enhances the anti-angiogenic effect of sunitinib in a preclinical renal cell carcinoma model

Angiogenesis, the formation of blood vessels from pre-existing ones, is an essential process in tumor growth and development. During angiogenesis, normal vessels consisting of endothelial and peri-endothelial cells are first destabilized via the Angiopoietin-2 (Ang-2)-Tie2 axis, and then endothelial cells are activated to proliferate and form new vessels mainly through the Vascular Endothelial Growth Factor (VEGF)-VEGFR2 axis. Currently there are several anti-angiogenic therapies targeting the VEGF-VEGFR pathway used in the clinic in various cancer settings. New therapies such as Ang-2 antagonists are also being pursued and have recently been shown to be valuable especially in combination with anti-VEGF therapies. Renal cell carcinoma (RCC) is a highly vascularized disease where anti-angiogenic therapies are used as both first and second line treatments. The present study focused on evaluating the effects of an Ang-2 antagonist in combination with the FDA approved Sunitinib, a first line treatment in RCC. An in vivo intradermal assay with VHL mutant, human renal cell carcinoma, Caki-2, cells was used to assess angiogenesis of either the Ang-2 antagonist, Sunitinib or the combination of the Ang-2 antagonist and Sunitinib. Results show a greater decrease in the number of tumor cell induced vessels in the Ang-2 and Sunitinib combination group compared to either Ang-2 antagonist or Sunitinib alone. Tumor growth was also impaired by these agents when used alone or in combination; however there was greater decrease in tumor volume in the Ang-2 and Sunitinib combination group compared to either Ang-2 antagonist or Sunitinib alone. These data show greater tumor vessel and tumor inhibition when an Ang-2 antagonist and Sunitinib are administered in combination. Citation Format: Nikolett Molnar, Dietmar W. Siemann. Angiopoietin-2 antagonist enhances the anti-angiogenic effect of sunitinib in a preclinical renal cell carcinoma model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5094. doi:10.1158/1538-7445.AM2013-5094