Abstract 4177: Inhibition of tumor malignancy by anti-angiogenic therapies in orthotopic mouse models of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy, and the third most common cause of cancer-related mortalities worldwide. Most cases occur in Asia, and in China alone an estimated 251,000 male and 95,000 female patients are diagnosed annually. Although significant advances have been made with the use of certain chemotherapeutic and targeted therapeutic agents in HCC treatment, the prognosis for most liver cancer patients remains poor. To address this significant unmet medical need, Pfizer Oncology has set out to strengthen its research and drug discovery activities targeting HCC. Here we report the establishment of two series (cell line-derived and primary human tumor-derived) of orthotopic mouse models of HCC, and their validation with anti-angiogenic compounds sutent and axitinib. In both series of models, tumor fragments obtained from in vivo expansion were surgically implanted into the left lobe of mouse liver to mimic the natural microenvironment and preserve the interaction between tumor cells and the stroma components. Both sutent and axitinib demonstrated significant anti-tumor activity, as well as metastatic potential at therapeutic doses. The anti-tumor activity of these agents are associated with reduction of CD31 in the tumor. Both sutent and axitinib were well tolerated by the animals during the course of the studies. In addition, plasma samples were collected at different time points for α-feto-protein (AFP) measurement. A significant correlation between tumor size (or weight) and serum AFP level was demonstrated, which indicated that circulating AFP can be utilized as a non-invasive biomarker for HCC burden. These results support anti-angiogenesis as a valid approach for effective treatment of HCC. 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 4177.