Molecular classification and novel targets in hepatocellular carcinoma: recent advancements.

Semin Liver Dis
Authors
Keywords
Abstract

Hepatocellular carcinoma (HCC) is one of most lethal cancers worldwide. Strategic decisions for the advancement of molecular therapies in this neoplasm require a clear understanding of its molecular classification. Studies indicate aberrant activation of signaling pathways involved in cellular proliferation (e.g., epidermal growth factor and RAS/mitogen-activated protein kinase pathways), survival (e.g., Akt/mechanistic target of rapamycin pathway), differentiation (e.g., Wnt and Hedgehog pathways), and angiogenesis (e.g., vascular endothelial growth factor and platelet-derived growth factor), which is heterogeneously presented in each tumor. Integrative analysis of accumulated genomic datasets has revealed a global scheme of molecular classification of HCC tumors observed across diverse etiologic factors and geographic locations. Such a framework will allow systematic understanding of the frequently co-occurring molecular aberrations to design treatment strategy for each specific subclass of tumors. Accompanied by a growing number of clinical trials of molecular targeted drugs, diagnostic and prognostic biomarker development will be facilitated with special attention on study design and with new assay technologies specialized for archived fixed tissues. A new class of genomic information, microRNA dysregulation and epigenetic alterations, will provide insight for more precise understanding of disease mechanism and expand the opportunity of biomarker/therapeutic target discovery. These efforts will eventually enable personalized management of HCC.

Year of Publication
2010
Journal
Semin Liver Dis
Volume
30
Issue
1
Pages
35-51
Date Published
2010 Feb
ISSN
1098-8971
URL
DOI
10.1055/s-0030-1247131
PubMed ID
20175032
PubMed Central ID
PMC3668687
Links
Grant list
P20 AA017067 / AA / NIAAA NIH HHS / United States
R01 DK037340 / DK / NIDDK NIH HHS / United States
R01 DK056601 / DK / NIDDK NIH HHS / United States
R01 DK076986 / DK / NIDDK NIH HHS / United States