Novel and Selective AMPK Activator for the Treatment of Hepatocellular Carcinoma

Project Summary/Abstract Liver cancer, primarily hepatocellular carcinoma (HCC), accounts for ~662,000 deaths each year and is the third leading cause of death from cancer worldwide. The age-adjusted incidence of HCC tripled between 1975 and 2005 in the US, and primary liver cancer mortality rates have increased faster than mortality for any other tumor type. One- and 3-year survival rates were 36% and 17%, respectively, in the Surveillance, Epidemiology and End Results (SEER) registries from 1998 to 2000.HCC is treated by aggressive surgery, liver transplantation, radiation, chemoembolization or chemotherapy. Only one drug (Nexavar/sorafenib) is approved for HCC and this extends life by a modest 4 months. The introduction of new and efficacious therapeuticoptions is critical for effective management of this disease, particularly in cases where tumor has spread to secondary sites. NovaTarg has established a novel approach to HCC treatment in which biguanides are designed to utilize transporters (OCT1 and O