News Note: An integrated DNA approach predicts therapeutic response in patients with advanced-stage liver cancer
NCI scientists have identified epigenetic and genetic signatures in liver cancer cells that may one day be used to predict clinical outcomes, with a high degree of accuracy, in patients with advanced-stage liver cancer. The incidence of liver cancer is increasing faster than that of other cancers in the United States. While early-stage liver cancer is amenable to potentially curative therapies, only about 30 percent of patients are diagnosed with early-stage disease. The new research addresses the needs of the subgroup of patients with advanced-stage disease who have few therapeutic options. Results of the study appear in the Oct. 20, 2010, Science Translational Medicine.
Liver tumors that progress from premalignant lesions to end-stage liver cancer are driven by genetic changes, as well as those indirectly related to the tumor’s DNA (epigenetic changes). Many epigenetic changes are reversible with the application of drugs, thereby offering a multi-target strategy against cancer. Zebularine inhibits an abnormal epigenetic activity called methylation that is frequently linked to cancer. In this study, the research team characterized the epigenetic changes induced by the drug zebularine in liver cancer cells. In an animal xenograft model (human tumor cells transplanted into mice) they found a distinct signature that identified two groups of tumor cell responses,those sensitive and those resistant to zebularine. Zebularine treatment of liver tumors bearing the sensitive profile resulted in increased survival and a decrease in metastasis to the lungs. Importantly, if this same result repeats itself in cancer patients, a zebularine sensitive signature could identify a subclass of patients—who today have poor survival and few treatment options—able to benefit from therapeutic agents that target the cancer epigenome.