Semin Liver Dis 2007; 27(1): 055-076
DOI: 10.1055/s-2006-960171
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Genomics and Signaling Pathways in Hepatocellular Carcinoma

Augusto Villanueva1 , Philippa Newell1 , Derek Y. Chiang2 , 3 , Scott L. Friedman1 , Josep M. Llovet1 , 4
  • 1Mount Sinai Liver Cancer Program, Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York
  • 2Broad Institute of MIT and Harvard, Cambridge, Massachusetts
  • 3Dana-Farber Cancer Institute, Boston, Massachusetts
  • 4BCLC Group, IDIBAPS, Liver Unit, Hospital Clinic, Barcelona, Spain
Further Information

Publication History

Publication Date:
12 February 2007 (online)


Hepatocellular carcinoma (HCC) is a leading cause of death among cirrhotic patients and has become a major health problem in developed countries. There is an elemental understanding of the genes and signaling pathways involved in the initiation and progression of this neoplasm. The current hypothesis of the HCC cell origin includes both somatic cells (hepatocytes) and stem cells/progenitor cells. Unlike that in other malignancies such as breast, brain, or hematopoietic cancers, the implication of cancer stem cells in HCC pathogenesis is not yet supported by consistent data. Analysis of somatic genetic alterations and gene expression profiles in HCC samples has provided relevant information on the genes involved in hepatocarcinogenesis, pinpointing a seminal molecular classification of the disease. Nonetheless, a comprehensive genomic analysis of HCC samples using high-resolution platforms in precisely annotated HCCs is clearly needed. Recent data have identified different signaling pathways in liver carcinogenesis (e.g., Wnt-βCatenin, Hedgehog, tyrosine kinase receptor-related pathways), providing an important potential source of novel molecular targets for new therapies. This review summarizes the most relevant information regarding structural and functional alterations in HCC and describes some of the key signaling pathways implicated in hepatocarcinogenesis.


Josep M Llovet, M.D. 

Division of Liver Diseases, Mount Sinai School of Medicine

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