Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 18, 2015; 7(5): 787-798
Published online Apr 18, 2015. doi: 10.4254/wjh.v7.i5.787
Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges
Gan-Lu Deng, Shan Zeng, Hong Shen
Gan-Lu Deng, Shan Zeng, Hong Shen, Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Hong Shen, Department of Oncology, Central South University, Changsha 410008, Hunan Province, China
Author contributions: Deng GL performed the research and wrote the draft paper; Zeng S collected the clinical information and analyzed the data; Shen H designed the research and revised the final version.
Supported by The grants from the National Nature Science Foundation of China, Nos. 30770971, 30800518, 81070362, 81172470 and 81372629; and two key projects from the Nature Science Foundation of Hunan Province, Nos. 11JJ2049 and 12JJ3118.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Hong Shen, Professor, Institute of Medical Sciences, Xiangya Hospital, Central South University, No 87, Xiangya Road, Changsha 410008, Hunan Province, China.
Telephone: +86-731-84327628 Fax: +86-731-84327633
Received: August 25, 2014
Peer-review started: August 26, 2014
First decision: September 28, 2014
Revised: October 26, 2014
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: April 18, 2015

Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis.

Keywords: Hepatocellular carcinoma, Ramucirumab, Regorafenib, Tivantinib, Molecular targeted therapy, Sorafenib, Linifanib, Erlotinib, Everolimus, Sunitinib, Brivanib

Core tip: Sorafenib is the first drug and now the only systemic treatment to prolong overall survival benefit in patients with hepatocellular carcinoma. In recent years, many molecular targeted agents have been developed and tested. This review article aims to summarize the efforts of systemic therapeutic options and explore the potential new systemic options for this disease.