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J Gastroenterol. 2009;44 Suppl 19:136-41. doi: 10.1007/s00535-008-2252-z. Epub 2009 Jan 16.

Molecular targeted therapy for hepatocellular carcinoma.

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Division of Hematology/Oncology Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.


A majority of patients with HCC present with advanced disease and are not candidates for liver transplantation, surgical resection, or regional therapy. Systemic cytotoxic chemotherapy agents are minimally effective, can have significant toxicity, and have not been shown to improve patient survival. Hepatocellular carcinomas are inherently chemotherapy-resistant tumors and are known to overexpress the multidrug resistance genes. Hepatocellular carcinoma is a very heterogeneous disease in terms of its etiology, molecular carcinogenic mechanisms, and biological behavior, which complicate our ability to identify rational molecular therapeutic "targets." Nearly every pathway involved in carcinogenesis is altered to some degree in HCC. Changes in hepatocyte growth factor expression, intracellular signaling, protease and matrix metalloproteinase expression, and oncogene expression are seen in HCC. The recent demonstration, in randomized clinical trials, of survival benefit for HCC patients treated with the oral agent sorafenib is encouraging progress in the development of molecularly targeted anticancer agents in HCC.

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