Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 8, 2015; 7(16): 2029-2040
Published online Aug 8, 2015. doi: 10.4254/wjh.v7.i16.2029
Optimal combination of antiangiogenic therapy for hepatocellular carcinoma
Hui-Ju Ch’ang
Hui-Ju Ch’ang, National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan
Hui-Ju Ch’ang, Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 100, Taiwan
Author contributions: Ch’ang HJ solely contributed to this manuscript.
Supported by National Health Research Institutes, Taiwan.
Conflict-of-interest statement: Nothing to declare.
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: Hui-Ju Ch’ang, MD, National Institute of Cancer Research, National Health Research Institutes, R1-2034, 35, Keyen Road, Miaoli 35053, Taiwan. hjmc@nhri.org.tw
Telephone: +886-37-246166-35105 Fax: +886-37-586463
Received: July 29, 2014
Peer-review started: July 30, 2014
First decision: December 17, 2014
Revised: July 21, 2015
Accepted: July 24, 2015
Article in press: July 27, 2015
Published online: August 8, 2015
Abstract

The success of sorafenib in prolonging survival of patients with hepatocellular carcinoma (HCC) makes therapeutic inhibition of angiogenesis a component of treatment for HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination of antiangiogenic agents with chemotherapy, radiotherapy or other targeted agents were evaluated. Nevertheless, the use of antiangiogenic therapy remains suboptimal regarding dosage, schedule and duration of therapy. The issue is further complicated by combination antiangiogenesis to other cytotoxic or biologic agents. There is no way to determine which patients are most likely respond to a given form of antiangiogenic therapy. Activation of alternative pathways associated with disease progression in patients undergoing antiangiogenic therapy has also been recognized. There is increasing importance in identifying, validating and standardizing potential response biomarkers for antiangiogenesis therapy for HCC patients. In this review, biomarkers for antiangiogenesis therapy including systemic, circulating, tissue and imaging ones are summarized. The strength and deficit of circulating and imaging biomarkers were further demonstrated by a series of studies in HCC patients receiving radiotherapy with or without thalidomide.

Keywords: Antiangiogenesis, Hepatocellular carcinoma, Biomarker, Cytokines, Dynamic contrast enhanced magnetic resonance imaging

Core tip: Antiangiogenic therapy has become an important component of treatment in hepatocellular carcinoma (HCC) patients. However, traditional anatomic imaging of tumor shrinkage is not appropriate to evaluate the efficacy of antiangiogenesis achieved by normalizing tumor vasculature and systemic suppression of angiogenic and inflammatory cytokines. To identify and validate potential response biomarkers, standardized systemic, circulating, tissue and imaging assays should be incorporated in to preclinical and clinical studies regarding the combination of antiangiogenic agents to cytotoxic or biologic agents. The optimal dosage, schedule and duration of antiangiogenic during combination therapy for HCC patients should be titrated according to these response biomarkers.