Korean J Hepatol.  2009 Sep;15(3):299-308. 10.3350/kjhep.2009.15.3.299.

Molecular targeting for treatment of advanced hepatocellular carcinoma

• Song IH

• KMID: 1374958
• DOI: http://doi.org/10.3350/kjhep.2009.15.3.299

Abstract

Hepatocellular carcinoma (HCC) is a major global health problem, which has a grave morbidity and mortality. Over the past few decades, no effective systemic therapeutic modalities have been established for patients with the unresectable HCC in advanced stage. Sorafenib is a small molecule that blocks cancer cell proliferation by targeting the intracellular signaling pathway at the level of Raf-1 and B-Raf serine-threonine kinases, and exerts an anti-angiogenic effect by targeting the vascular endothelial growth factor receptor-1, 2 and 3, and platelet-derived growth factor receptor-beta tyrosine kinases. Recently, two clinical successful applications, SHARP and Asia-Pacific trial, of multikinase inhibitor sorafenib represent a significant advance in the treatment of advanced HCC patients without a curative chance. However, because the results of clinical trials show diverse responses in a subset of HCC patients, a molecular classification of HCC through the excavation of specific biomarkers related to its biological behavior is necessary for sorting HCC patients to each group with a biological homogeneity, ultimately leading to the most suitable individualization of molecular targeted therapy in HCC.

Keyword

Hepatocellular carcinoma; Molecular targeted therapy; Sorafenib; Hepatocarcinogenesis; Signaling pathway

MeSH Terms

Antineoplastic Agents/therapeutic use
Benzenesulfonates/therapeutic use
Carcinoma, Hepatocellular/pathology/secondary/*therapy
Humans
Liver Neoplasms/blood supply/pathology/*therapy
Neovascularization, Pathologic
Proto-Oncogene Proteins B-raf/antagonists & inhibitors/metabolism
Proto-Oncogene Proteins c-raf/antagonists & inhibitors/metabolism
Pyridines/therapeutic use
Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors/metabolism
Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors/metabolism
Signal Transduction