Glucose Metabolism and Oxidative Stress in Hepatocellular Carcinoma: Role and Possible Implications in Novel Therapeutic Strategies

Abstract

Hepatocellular carcinoma (HCC) metabolism is redirected to glycolysis to enhance the production of metabolic compounds employed by cancer cells to produce proteins, lipids, and nucleotides in order to maintain a high proliferative rate. This mechanism drives towards uncontrolled growth and causes a further increase in reactive oxygen species (ROS), which could lead to cell death. HCC overcomes the problem generated by ROS increase by increasing the antioxidant machinery, in which key mechanisms involve glutathione, nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible transcription factor (HIF-1α). These mechanisms could represent optimal targets for innovative therapies. The tumor microenvironment (TME) exerts a key role in HCC pathogenesis and progression. Various metabolic machineries modulate the activity of immune cells in the TME. The deregulated metabolic activity of tumor cells could impair antitumor response. Lactic acid–lactate, derived from the anaerobic glycolytic rate of tumor cells, as well as adenosine, derived from the catabolism of ATP, have an immunosuppressive activity. Metabolic reprogramming of the TME via targeted therapies could enhance the treatment efficacy of anti-cancer immunotherapy. This review describes the metabolic pathways mainly involved in the HCC pathogenesis and progression. The potential targets for HCC treatment involved in these pathways are also discussed.

<p>Effects of LRP1B Regulated by HSF1 on Lipid Metabolism in Hepatocellular Carcinoma</p>

“…9,10,37 Notably, metabolic alteration is being regarded as a key hallmark of liver cancer but still remains unclear in HCC. 10,38 Previous well-studied metabolic alterations in HCC are mainly glucose, glutamine and methionine metabolism, [39][40][41] less attention has been paid to lipid metabolism features of HCC. As obesity-and NAFLD-related HCC cases increase in China, it is urgent to exploit the patterns and influences of lipid metabolism in HCC.…”

New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics

“…Metabolic adaptation is a central factor that contributes to ensuring the supply of cellular building blocks including proteins, lipids, and nucleotides in order to maintain a high proliferative rate of HCC [ 54 ]. In this regards, miR-29a has been reported to act toward genes involved in metabolism to impede HCC progression.…”

Identification and validation of redox-immune based prognostic signature for hepatocellular carcinoma

“…Therefore, a signature established by the union of different cancer hallmarks would devote to the patient's classification, which may benefit prognosis prediction and development of targeted treatment tactics. Oxidative stress is a trait of many cancers, including HCC, which plays a crucial role in regulating metabolism, cell proliferation, and immune response in HCC 28 . Here, we developed a 14-gene signature based on redox and immune-related markers for prognosis prediction of HCC.…”