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World J Gastroenterol. Nov 7, 2014; 20(41): 15269-15274
Published online Nov 7, 2014. doi: 10.3748/wjg.v20.i41.15269
Downregulation of signal transducer and activator of transcription 3 by sorafenib: A novel mechanism for hepatocellular carcinoma therapy
Man-Hsin Hung, Wei-Tien Tai, Chung-Wai Shiau, Kuen-Feng Chen
Man-Hsin Hung, Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
Man-Hsin Hung, Program in Molecular Medicine, School of Life Sciences, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
Wei-Tien Tai, Kuen-Feng Chen, Department of Medical Research, National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei 100, Taiwan
Chung-Wai Shiau, Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
Author contributions: Hung MH wrote the manuscript and generated the figures; Tai WT and Shiau CW contributed to the writing and editing of the manuscript; Chen KF generated the idea and designed the aims of this review and wrote the manuscript.
Correspondence to: Kuen-Feng Chen, MD, PhD, Department of Medical Research, National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. kfchen1970@ntu.edu.tw
Telephone: +886-2-23123456 Fax: +886-2-23225329
Received: March 19, 2014
Revised: May 7, 2014
Accepted: June 12, 2014
Published online: November 7, 2014
Core Tip

Core tip: Hepatocellular carcinoma (HCC) is one of the major cancers worldwide, for which the only approved target therapy is sorafenib. In addition to its previously characterized kinase inhibition, sorafenib also acts via a kinase-independent mechanism to target signal transducer and activator of transcription 3 (STAT3) signaling in HCC cells. This review discusses these findings, adding to the knowledge concerning the mechanisms of action of sorafenib as well as exploring the potential use of STAT3 as a therapeutic target in future cancer drug development.