Molecular targeting for treatment of advanced hepatocellular carcinoma.
10.3350/kjhep.2009.15.3.299
- Author:
Il Han SONG
1
Author Information
1. Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea. ihsong21@dankook.ac.kr
- Publication Type:Review
- Keywords:
Hepatocellular carcinoma;
Molecular targeted therapy;
Sorafenib;
Hepatocarcinogenesis;
Signaling pathway
- MeSH:
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
- From:The Korean Journal of Hepatology
2009;15(3):299-308
- CountryRepublic of Korea
- Language:English
-
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.
