Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect

Area of Science:

• Oncology
• Metabolic pathways
• Tumor microenvironment

Background:

• Hepatocellular carcinoma (HCC) is a prevalent cancer with poor prognosis, often diagnosed at advanced stages.
• The tumor microenvironment (TME) in HCC, characterized by hypoxia, acidosis, and immune suppression, promotes aerobic glycolysis (Warburg effect).
• This glycolysis exacerbates TME conditions, driving HCC proliferation, angiogenesis, invasion, and metastasis.

Purpose of the Study:

• To review the intricate mechanisms linking the TME, glycolysis, and gluconeogenesis in HCC progression.
• To explore the potential of targeting gluconeogenesis as a therapeutic strategy for HCC.
• To discuss current HCC treatments and future therapeutic directions.

Main Methods:

• Literature review of studies on HCC, TME, glycolysis, and gluconeogenesis.
• Analysis of the interplay between metabolic reprogramming and HCC pathogenesis.
• Examination of existing and emerging therapeutic interventions for advanced HCC.

Main Results:

• The Warburg effect is a key metabolic adaptation in HCC, driven by the TME.
• Gluconeogenesis has emerged as a mechanism to inhibit glycolysis and impede HCC progression.
• Sorafenib remains a primary treatment, but novel metabolism-related targets are crucial.

Conclusions:

• A deeper understanding of the TME-glycolysis-gluconeogenesis axis is vital for HCC treatment.
• Targeting gluconeogenesis and the Warburg effect presents promising therapeutic avenues.
• Combination therapies involving sorafenib, TME modulation, and anti-Warburg strategies are likely future directions for advanced HCC treatment.