Metabolic reprogramming and its clinical implication for liver cancer

Area of Science:

• Oncology
• Metabolic pathways
• Cancer biology

Background:

• Cancer cells adapt to nutrient-poor environments via metabolic reprogramming, a hallmark fueling tumor growth, metastasis, and drug resistance.
• Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) exhibit significant heterogeneity, yet often display altered glycolysis and lactate production (Warburg effect).
• Non-alcoholic fatty liver disease (NAFLD) is an emerging major cause of liver cancer, necessitating a focus on its metabolic implications.

Approach:

• This review synthesizes current knowledge on common and subset-specific metabolic alterations in HCC and CCA.
• It examines the metabolic landscape of NAFLD in the context of liver cancer development.
• The review highlights the clinical relevance of liver cancer metabolism and computational approaches for identifying therapeutic targets.

Key Points:

• Metabolic reprogramming is crucial for cancer cell adaptation and survival.
• Liver cancer metabolism is heterogeneous, with commonalities like the Warburg effect and subset-specific dependencies (e.g., fatty acid catabolism in some HCCs).
• NAFLD-associated liver cancer presents unique metabolic challenges.

Conclusions:

• Understanding the diverse metabolic profiles of liver cancers, including those linked to NAFLD, is critical for clinical management.
• Computational and systems biology tools, like metabolic models, offer powerful avenues for discovering personalized therapeutic strategies.
• Targeting metabolic vulnerabilities holds promise for improving treatment outcomes in liver cancer patients.