Cancer

Cell culture and mouse studies suggest inhibiting the HMG-CoA reductase/SQLE/LSS pathway could help treat p53-deficient liver cancer. In human liver adenocarcinoma cell lines, levels of two metabolic intermediates biosynthesized by the pathway -- phosphomevalonate and diphosphomevalonate -- were higher in cells with p53 knocked out than in cells with normal p53 expression. In a p53-deficient mouse model of hepatocellular carcinoma (HCC), the HMG-CoA reductase inhibitor Lipitor atorvastatin or shRNAs targeting HMG-CoA reductase, SQLE or LSS decreased tumor numbers in the liver compared with vehicle or a non-specific shRNA. Next steps could include identifying and testing additional inhibitors of the pathway in models of p53-deficient liver cancer...