Issues

Metabolic reprogramming has been included in the hallmarks of cancer models, so that targeting cancer metabolism has attracted a great deal of attention to cancer prevention as well as cancer therapeutics. Hepatocellular carcinoma (HCC) is a highly lethal tumor with nearly 600,000 deaths each year worldwide partly due to a high recurrence rate. In this study, metabolic alteration at the initiation step of diethylnitrosamine (DEN)-induced hepatic tumorigenesis was investigated in an attempt to gain more insights into the chemoprevention of HCC. The cover figure depicts a general overview of the major metabolic pathways of the livers in obese and diabetic C57BKSL/J- +Lepr^db/+Lepr^db mice (^db/db mice) administered DEN and/or acyclic retinoid (ACR), which is a promising drug in clinical trials for preventing recurrence of HCC. Of interest, alterations in lipid metabolism but not glucose metabolism were observed in DEN-induced hepatic tumorigenesis. ACR significantly counteracted against acceleration of linoleic acid metabolites such as arachidonic acid, a pro-inflammatory precursor, suggesting an important role of lipid metabolism reprogramming leading to chronic inflammation in the initiation step of hepatic tumorigenesis. See the article by Qin and colleagues (beginning on page 205) for more information.