Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

Area of Science:

• Hepatology
• Oncology
• Cancer Stem Cell Biology

Background:

• Liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), is a significant cause of cancer mortality.
• These cancers often arise in the context of liver cirrhosis, non-alcoholic fatty liver disease, and chronic liver damage.
• Hepatocarcinogenesis is a multi-step process involving the transformation of pre-cancerous lesions into HCC, influenced by various etiologies like viral infections, alcohol abuse, and metabolic syndrome.

Purpose of the Study:

• To elucidate the genomic alterations in liver tumors for targeted therapy development.
• To define and characterize liver cancer stem cells (LCSCs) as a critical component of liver cancer.
• To identify robust methods for the isolation and identification of LCSCs.

Main Methods:

• Genomic profiling of HCC and iCCA tumors.
• Isolation and characterization of liver cancer stem cells based on specific cell surface proteins (e.g., CD133, CD90, CD44, EpCAM) and functional markers (e.g., side population, aldehyde dehydrogenase activity).
• Utilizing immunophenotypic and functional assays to define LCSCs.

Main Results:

• Genomic alterations in liver tumors have been identified, providing insights for potential targeted therapies.
• Liver cancer stem cells are characterized by specific cell surface proteins and functional properties.
• A combination of immunophenotypic and functional assessments is necessary for accurate identification and definition of LCSCs.

Conclusions:

• Understanding the molecular landscape of liver cancer is crucial for advancing therapeutic strategies.
• Liver cancer stem cells play a pivotal role in tumor initiation, metastasis, relapse, and chemoresistance.
• The precise identification of LCSCs using defined markers is essential for developing effective treatments and improving patient survival in liver cancer.