Combined anti-angiogenic therapy against VEGF and integrin alphabeta in an orthotopic model of ovarian cancer

Abstract

Purpose: We tested the efficacy of dual targeting of vascular endothelial growth factor (VEGF) and the alphavbeta3 integrin in orthotopic mouse models of ovarian cancer. Experimental Design: In vivo therapy experiments were conducted in chemo-sensitive (SKOV3ip1, HeyA8) and -resistant (SKOV3TRip2) ovarian cancer models. VEGF was targeted with bevacizumab and alphavbeta3 with etaracizumab. Mice were treated with each agent alone, together, or in combination with paclitaxel for assessment of tumor growth. Tumor specimens were tested for proliferative index, microvessel density, and apoptosis. Results: In the SKOV3ip1 model, both single-agent bevacizumab and etaracizumab reduced tumor growth by 52-63% (p