Improvement in the Current Therapies for Hepatocellular Carcinoma Using a Systems Medicine Approach

Area of Science:

• Oncology
• Genomics
• Metabolomics

Background:

• Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality due to limited targeted therapies.
• Current HCC treatments, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, are relatively uniform.
• There is a critical need for novel therapeutic strategies targeting HCC's specific molecular and metabolic dysregulations.

Purpose of the Study:

• To review current and emerging therapeutic targets for HCC.
• To highlight the role of molecular profiling and metabolic network-based strategies in HCC treatment.
• To emphasize the potential for personalized medicine in HCC management.

Main Methods:

• Integrative genomic profiling to identify frequently mutated genes and molecular targets (e.g., telomerase reverse transcriptase, TP53, CTNNB1).
• Application of genome-scale metabolic models to understand cancer-specific metabolism.
• Analysis of metabolic network-driven patient stratification based on redox responses and metabolic pathways.

Main Results:

• Consistent upregulation of de novo lipogenesis is essential for HCC cell proliferation.
• Molecular profiling reveals key targets including telomerase reverse transcriptase, TP53, and CTNNB1.
• Metabolic network analysis enables stratification of HCC patients for personalized treatment approaches.

Conclusions:

• Targeting molecular and metabolic pathways offers promising avenues for effective HCC therapy.
• Genome-scale metabolic models are valuable tools for discovering drug targets and biomarkers in HCC.
• Personalized medicine strategies informed by molecular and metabolic profiling can improve HCC treatment outcomes.