Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors

Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing an tibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demo nstrated independently that these agents can inhibit tumour growth and indu ce apoptosis in colon cancer in in vivo and in vitro systems. We hypothesiz ed that simultaneous blockade of the VEGF and EGF receptors would enhance t he therapy of colon cancer in a mouse model of peritoneal carcinomatosis. N ude mice were given intraperitoneal injection of KM12L4 human colon cancer cells to generate peritoneal metastases. Mice were then randomized into one of four treatment groups: control, anti-VEGFR (DC101), anti-EGFR (C225), o r DC101 and C225. Relative to the control group, treatment with DC101 or wi th DC101+C225 decreased tumour vascularity, growth, proliferation, formatio n of ascites and increased apoptosis of both tumour cells and endothelial c ells. Although C225 therapy did not change any of the above parameters, C22 5 combined with DC101 led to a significant decrease in tumour vascularity a nd increases in tumour cell and endothelial cell apoptosis (vs the DC101 gr oup). These findings suggest that DC101 inhibits angiogenesis, endothelial cell survival, and VEGF-mediated ascites formation in a murine model of col on cancer carcinomatosis. The addition of C225 to DC101 appears to lead to a further decrease in angiogenesis and ascites formation. Combination anti- VEGF and anti-EGFR therapy may represent a novel therapeutic strategy for t he management of colon peritoneal carcinomatosis. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.