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2014 ; 1
(2
): 76-83
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Hepatocellular Carcinoma: Basic and Transitional Research
#MMPMID26675991
Yin C
; Xie WF
Gastrointest Tumors
2014[Jun]; 1
(2
): 76-83
PMID26675991
show ga
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of
cancer-related deaths worldwide. The outcome of HCC therapy depends on the stage
of HCC. Early-stage HCC patients can be cured with radical treatment approaches,
whereas no standard treatment regimens can be recommended for patients with
advanced disease. SUMMARY: In-depth basic research into the molecular mechanisms
of HCC has contributed to the development of novel therapeutic agents. This
article reviews several key classes of novel therapeutic agents that are under
development, including molecular-targeted therapies, cancer stem cell (CSC)-based
therapy and differentiation therapy. KEY MESSAGE: A greater understanding of the
molecular pathogenesis of HCC has contributed to the development of novel
therapeutic agents. This article reviews several key classes of novel therapeutic
agents that are under development, including molecular-targeted therapies,
CSC-based therapy and differentiation therapy. PRACTICAL IMPLICATIONS:
Molecular-targeted therapies based on signaling pathways involved in
hepatocarcinogenesis and progression are being evaluated in several clinical
trials. There are three main categories of targeted agents: tyrosine kinase
inhibitors (TKIs), monoclonal antibodies and enzyme inhibitors. The
best-established agent is sorafenib, a non-specific TKI that is accepted as
first-line therapy for specific patients. Other similar agents under
investigation include erlotinib, linifanib and brivanib. CSC-based therapies are
still in the earlier stages of development and include a neutralizing anti-CD44
antibody, small interfering RNA to suppress epithelial cell adhesion molecular
levels, a neutralizing anti-CD13 antibody and a CD13 inhibitor. An important
point is that CSC-targeted therapy should be combined with conventional therapies
to achieve complete tumor regression. Differentiation therapy is defined as a
strategy that induces malignant reversion of tumor cells. Hepatocyte nuclear
factor 4? or 1?, important transcriptional factors for hepatocyte differentiation
and phenotype maintenance, have shown significant antitumor effects by inducing
differentiation of both non-CSCs and CSCs in HCC towards a hepatocyte-like
phenotype.
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