Glucose intolerance and hepatocellular carcinoma: recent findings for old diseases

In the last years, an increasing number of evidences on the influence of metabolic syndrome on theoccurrence of hepatocellular carcinoma (HCC) have been developed. Type 2 mellitus diabetes (T2MD) hasbeen found to increase the occurrence of primary liver tumors and to define a more aggressive carcinogeneticprocess. Furthermore, several preclinical and observational studies and a recent meta-analysis have shownthat anti-diabetic drugs can modify the risk of HCC development in patients with T2DM. However, despitethese evidences, underlying molecular mechanisms linking both pathological conditions have to be completelycleared yet. The study published by Gao et al. has found a possible molecular link between the two conditions,describing the predisposition to T2DM and HCC given by the haploinsufficiency of nuclear receptorcoactivator 5 (NCOA5) in murine models. The authors have generated Ncoa5+/– (haploinsufficient) malemice and shown that 94% of male mutant mice developed HCC within 18 months of age, this in contrast withNcoa5+/+ and Ncoa5+/– female mice. These results suggest that NCOA5 haploinsufficiency is linked to HCCdevelopment in male mice. Moreover, mutant male mice showed significantly elevated levels of fasting bloodglucose and markedly decreased glucose tolerance and insulin sensitivity compared to Ncoa5+/+ littermates. This well-constructed work sheds light on the molecular link between T2DM and HCC and opens the way tofurther biological and clinical studies in the field of liver tumor prevention and treatment.