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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2015; 21(36): 10336-10347
Published online Sep 28, 2015. doi: 10.3748/wjg.v21.i36.10336
Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?
Yu-Yun Shao, Chih-Hung Hsu, Ann-Lii Cheng
Yu-Yun Shao, Chih-Hung Hsu, Ann-Lii Cheng, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 10051, Taiwan
Yu-Yun Shao, Chih-Hung Hsu, Department of Oncology, National Taiwan University Hospital, Taipei 10002, Taiwan
Ann-Lii Cheng, Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan
Author contributions: Shao YY and Hsu CH collected data; Shao YY, Cheng AL, and Hsu CH wrote the paper.
Supported by Grants from National Science Council, Taiwan No. NSC-101-2314-B-002-141 and No. NSC-102-2314-B-002-120; and Ministry of Science and Technology, Taiwan, No. MOST-103-2314-B-002-181-MY2, No. MOST-103-2314-B-002-090 and No. MOST -103-2314-B-002-092.
Conflict-of-interest statement: Yu-Yun Shao has nothing to declare. Chih-Hung Hsu has received fees for serving as a speaker from Bayer, and a consultant for Bayer, Exelixis, and Roche. Ann-Lii Cheng was a consultant of Novartis, Merck Serono, Eisai, Exelixis, and GlaxosmithKline LLC, and received research funding from Sanofi (China) and Chugai Pharma R&D Taiwan Ltd.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Chih-Hung Hsu, MD, PhD, Department of Oncology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 10002, Taiwan. chihhunghsu@ntu.edu.tw
Telephone: +886-2-23123456-67680 Fax: +886-2-23711174
Received: March 24, 2015
Peer-review started: March 26, 2015
First decision: May 18, 2015
Revised: May 26, 2015
Accepted: August 28, 2015
Article in press: August 31, 2015
Published online: September 28, 2015
Abstract

Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However, efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2, hepatocyte growth factor, insulin-like growth factor-1, and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast-enhanced magnetic resonance imaging, and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC.

Keywords: Hepatocellular carcinoma, Predictive marker, Prognosis, Sorafenib

Core tip: A predictive biomarker of sorafenib efficacy in advanced hepatocellular carcinoma is a clinical unmet need. Previous studies identified the potential of blood levels of angiopoietin-2, hepatocyte growth factor, insulin-like growth factor-1, and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast-enhanced magnetic resonance imaging, and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new research directions. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced hepatocellular carcinoma.