Abstract 375: Targeting pericytes in ovarian carcinoma

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Abstract Purpose: Pericytes interact with and closely regulate endothelial cell function. Platelet-derived growth factor (PDGF)-BB/PDGF receptor (PDGFR) β plays a critical role in pericyte regulation, therefore highly specific inhibitors of this target are needed. We hypothesize that dual targeting of endothelial cells and pericytes provide a more efficacious antiangiogenic approach for ovarian cancer therapy. Experimental Design: The therapeutic efficacy of targeting endothelial cells (bevacizumab) and/or pericytes (PDGF-aptamer, AX102) was examined using SKOV3ip1 and HeyA8 orthotopic ovarian cancer models. The biomarkers, such as microvessel density (MVD), vascular maturation (pericyte coverage), and proliferative index (proliferating cell nuclear antigen, PCNA) were examined. Results: Bevacizumab inhibited tumor growth by 48% and 45% in the SKOV3ip1 and HeyA8 models, respectively. AX102 had minimal effect on the HeyA8 model, but increased tumor growth in the SKOV3ip1 model. However, bevacizumab plus AX102 was more effective than bevacizumab alone, and reduced 76 - 88% of tumor growth in both models. A longitudinal study using bioluminescence imaging in the HeyA8 model showed that a combination of bevacizumab, AX102 and paclitaxel caused tumor reduction by 65% (based on bioluminescence imaging). MVD and proliferative index counts were significantly reduced in the bevacizumab treatment groups, and pericyte coverage was significantly decreased in the AX102 treatment groups. Conclusions: Dual targeting of endothelial cells and pericytes demonstrates therapeutic potential as a unique anti-vascular approach in treating ovarian carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 375.