Oxidative stress in obesity-associated hepatocellular carcinoma: sources, signaling and therapeutic challenges

Obesity affects more than 650 million individuals worldwide and is a well-established risk factor for the development of hepatocellular carcinoma (HCC). Oxidative stress can be considered as a bona fide tumor promoter, contributing to the initiation and progression of liver cancer. Indeed, one of the key events involved in HCC progression is excessive levels of reactive oxygen species (ROS) resulting from the fatty acid influx and chronic inflammation. This review provides insights into the different intracellular sources of obesity-induced ROS and molecular mechanisms responsible for hepatic tumorigenesis. In addition, we highlight recent findings pointing to the role of the dysregulated activity of BCL-2 proteins and protein tyrosine phosphatases (PTPs) in the generation of hepatic oxidative stress and ROS-mediated dysfunctional signaling, respectively. Finally, we discuss the potential and challenges of novel nanotechnology strategies to prevent ROS formation in obesity-associated HCC.

Automated summary

Obesity is a well-established risk factor for hepatocellular carcinoma, with oxidative stress playing a key role in the initiation and progression of liver cancer. Excessive levels of reactive oxygen species (ROS) from fatty acid influx and chronic inflammation are major contributors to HCC progression. Dysregulated activity of BCL-2 proteins and protein tyrosine phosphatases (PTPs) are implicated in hepatic oxidative stress and dysfunctional signaling mediated by ROS.