Integrated DNA Strategy Predicts Therapeutic Response in Advanced-stage Liver Cancer Patients

US scientists have identified epigenetic and genetic signatures in liver cancer cells that may in the near future be used to predict clinical outcomes, with a high level 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% 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 choices. The study's findings were published in the October 20, 2010, issue of the journal 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 alterations). Many epigenetic changes are reversible with the application of drugs, thereby offering a multitarget approach against cancer.

According to investigators from the U.S. National Cancer Institute (NCI; Bethesda, MD, USA) Zebularine inhibits an abnormal epigenetic activity called methylation that is frequently linked to cancer. In this study, the researchers characterized the epigenetic changes induced by the drug zebularine in liver cancer cells. In an animal xenograft model in which human tumor cells transplanted into mice, they discovered 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.

Significantly, if this same result repeats itself in cancer patients, according to the scientists, a zebularine-sensitive signature could identify a subclass of patients--who up to now have poor survival and few treatment options--able to benefit from therapeutic agents that target the cancer epigenome.

Related Links:
National Cancer Institute