Abstract 2776: Overexpression of HGF is an effective indicator for Met-targeting therapy in hepatocellular carcinoma

The success of molecular targeted therapy against cancer depends on discovering the essential pathways that contribute to carcinogenesis and cancer progression and the molecular targets that control the pathway activity. By using genetically engineered mouse models, we show that overexpression of Hepatocyte growth factor (HGF) stimulated HBV surface antigen (HBsAg) production and accelerated the HCC progression. HGF transgenic mouse model produced spontaneous HCC with genomic profiles similar to that HBV-positive HCC patients with poor prognosis. Mechanistically, MET receptor expression is required for repair of virus-induced liver damage and HCC development. Importantly, HGF overexpression induces an autocrine activation which determines the sensitivity to small-molecule Met inhibitors. MET inhibitors are entering clinical trials against cancer, and our data provide a molecular basis for targeting the Met pathway in hepatitis B-induced HCC. Our results demonstrate that HGF is a driver of HBV-induced HCC progression and may serve as an effective biomarker for Met-targeted therapy, and that hgf-transgenic mouse model serves as a good tool for studying human HCC biology and preclinical evaluating therapeutics. Citation Format: Qian Xie. Overexpression of HGF is an effective indicator for Met-targeting therapy in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2776. doi:10.1158/1538-7445.AM2014-2776