Review
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World J Gastroenterol. Feb 14, 2012; 18(6): 498-506
Published online Feb 14, 2012. doi: 10.3748/wjg.v18.i6.498
Targeted systemic therapies for hepatocellular carcinoma: Clinical perspectives, challenges and implications
Catherine Frenette, Robert Gish
Catherine Frenette, Robert Gish, California Pacific Medical Center, San Francisco, CA 94115, United States
Author contributions: Frenette C and Gish R contributed equally to the writing of this manuscript.
Correspondence to: Catherine Frenette, MD, Medical Director of Liver Transplantation, Director of Liver Cancer Program, The Methodist Hospital, Houston, TX 77030, United States. ctfrenette@tmhs.org
Telephone: +1-713-4410179 Fax: +1-731-4415248
Received: February 21, 2011
Revised: June 6, 2011
Accepted: June 13, 2011
Published online: February 14, 2012
Abstract

Hepatocellular carcinoma (HCC) is a lethal disease in most patients, due to its aggressive course and a lack of effective systemic therapies for advanced disease. Surgical resection and liver transplantation remain the only curative options for a small subset of patients. Few patients with HCC are diagnosed early enough to be eligible for curative treatment. Angiogenesis inhibition is a natural therapeutic target for all solid tumors, but particularly for the highly vascularized HCC tumors. With the approval of the targeted agent sorafenib, there are now additional options for patients with HCC. Although sorafenib does produce some improvement in survival in HCC patients, the responses are not durable. In addition, there are significant dermatologic, gastrointestinal, and metabolic toxicities, and, as importantly, there is still limited knowledge of its usefulness in special subpopulations with HCC. Other angiogenesis inhibitors are in development to treat HCC both in the first-line setting and for use following sorafenib failure; the furthest in development is brivanib, a dual fibroblast growth factor pathway and vascular endothelial growth factor receptor inhibitor. Additional agents with antiangiogenic properties also in phase II and III development for the treatment of patients with HCC include bevacizumab, ramucirumab, ABT-869, everolimus and ARQ 197.

Keywords: Hepatocellular carcinoma; Angiogenesis; Vascular endothelial growth factor; Fibroblast growth factor; Sorafenib; Tumor response; Brivanib