Special Issue "Targeted Therapy of Hepatocellular Carcinoma: Present and Future"


A special issue of Diseases (ISSN 2079-9721).

Deadline for manuscript submissions: closed (20 August 2015)

Special Issue Editor

Guest Editor
Dr. Stephen L. Chan
Department of Clinical Oncology, Prince of Wales Hospital, Shatin, HKSAR, China
Phone: 852-26322118
Interests: hepatocellular carcinoma; pancreatic cancer; biliary tract cancer; biomarker; inflammation; targeted therapy

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Drug development for HCC used to be slow due to the relative chemo-refractoriness of the tumor and underlying co-morbid cirrhosis in most patients. Since 2008, clinical trial results on sorafenib have led to development of molecular targeted agents for HCC. For the past 5 years, a number of tyrosine kinase inhibitors have completed phase III testing but all of them have turned out to be negative. These studies persistently reported a median overall survival of 9 to 10 months, indicating that the benefit of an existing panel of targeted agents may have reached a plateau for advanced HCC. To overcome this deadlock, novel agents and concepts are needed from researchers of the HCC research world.

This Special Issue provides an Open Access opportunity to publish research and review articles on targeted therapy for HCC. The focus will be put on a comprehensive review of the current literatures as well as insights into the improvement of success rate of clinical trials on novel agents for the aggressive tumor.

Dr. Stephen L. Chan
Guest Editor


Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diseases is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.


  • hepatocellular carcinoma
  • sorafenib
  • clinical trial
  • targeted agent
  • cirrhosis
  • hepatitis

Published Papers (4 papers)

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Displaying article 1-4
p. 150-158
by , , , , ,  and
Diseases 2015, 3(3), 150-158; doi:10.3390/diseases3030150
Received: 20 May 2015 / Revised: 13 July 2015 / Accepted: 13 July 2015 / Published: 22 July 2015
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(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
p. 68-77
by , , , , , ,  and
Diseases 2015, 3(2), 68-77; doi:10.3390/diseases3020068
Received: 26 March 2015 / Revised: 19 April 2015 / Accepted: 6 May 2015 / Published: 15 May 2015
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(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
p. 226-242
by ,  and
Diseases 2014, 2(3), 226-242; doi:10.3390/diseases2030226
Received: 11 April 2014 / Revised: 10 June 2014 / Accepted: 2 July 2014 / Published: 7 July 2014
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(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
p. 209-225
by , , ,  and
Diseases 2014, 2(3), 209-225; doi:10.3390/diseases2030209
Received: 16 April 2014 / Revised: 24 June 2014 / Accepted: 25 June 2014 / Published: 1 July 2014
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(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of the Paper: Review
Title: A role of acyclic retinoid in the chemoprevention of hepatocellular carcinoma: Therapeutic strategy targeting phosphorylated retinoid X receptor-α
Authors: Hiroyasu Sakai, Masahito Shimizu and Hisataka Moriwaki *
Affiliations: Department of Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; E-Mails: sakai-hiroyasu@hotmail.co.jp (H.S.); hmori@gifu-u.ac.jp (H.M.) Author to whom correspondence should be addressed; E-Mail: shimim-gif@umin.ac.jp; Tel.: +81-58-230-6313; Fax: +81-58-230-6310.
Abstract: Hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis due to its high rate of recurrence after initial treatment. Therefore, the development of effective therapeutic strategies that can prevent recurrence and secondary tumor formation will improve the clinical outcome of HCC patients. A malfunction of the retinoid X receptor-α (RXRα) due to the activation of the Ras-MAPK signaling pathway is highly associated with hepatocarcinogenesis. Acyclic retinoid (ACR), which is one of synthetic retinoids, prevents HCC recurrence by inhibiting Ras-MAPK activation and subsequent RXRα phosphorylation, thus improving patient prognosis. Here, we review the detailed effects of ACR on the prevention of HCC development, based on the results of our basic and clinical research.

Type of Paper: Review
Title: Radiological Assessment of Antiangiogenic Therapies for Hepatocellular Carcinoma: Which Criteria Apply?
Authors: Mohamed Bouattour 1,*, onorina Bruno 2 and Johanna Wassermann 3
1 Department of Hepatology. Hôpital Beaujon ; 100 Boulevard du Général Leclerc. 92110 Clichy, France
2 Department of Radiology. Hôpital Beaujon; 100 Boulevard du Général Leclerc. 92110 Clichy, France
3 Department of Medical Oncology. Hôpital Pitié-Salpêtrière; 47-83 boulevard de l'Hôpital
75013 Paris, France
Author to whom correspondence should be addressed; E-Mail: mohamed.bouattour@bjn.aphp.fr; Tel.: +33 1 40 87 55 25; Fax: +33 1 47 39 61 78
Abstract: The sorafenib, an oral multi-tyrosine kinase inhibitor, is currently approved by regulatory agencies as the standard-of-care first-line treatment of advanced hepatocellular carcinoma (HCC). Sorafenib is the first and so far the sole drug that has shown overall survival benefit in patients with advanced HCC in two III trials. The remarkable results obtained by sorafenib are contrasting with objective response rate inferior to 5% according to RECIST criteria. Distinct to standard chemotherapies, low objective response rates were also observed with other antiangiogenic agents tested in HCC. Tumor shrinkage and dimensional changes, usually assessed to define response to cytotoxic drugs based on morphological RECIST criteria, were rarely observed in patients treated with antiangiogenic therapies. Hence, Radiological evaluation of efficacy using standard RECIST criteria is often inappropriate to assess response to targeted agents in HCC patients. Alternatives criteria of response, such as mRECIST, EASL and CHOI criteria have been proposed to assess the direct effect of antianagiogenic therapies in HCC. In this review, we purpose to analyze relevance of these new criteria in clinical practice and their performance to predict response of antiangiogenic therapies for HCC.

Type of Paper: Review
Title: Role of MTDH, FOXM1 and microRNAs in drug resistance in hepatocellular carcinoma
Authors: Xiangbing Meng 1,2,*, Eric J Devor 1, Shujie Yang 1 and Kimberly K Leslie 1,2
1 Departments of Obstetrics and Gynecology, The University of Iowa, Iowa City, Iowa 52242, USA
Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, Iowa 52242, USA Author to whom correspondence should be addressed; E-Mail: xiangbing-meng@uiowa.edu
Abstract: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies due to underlying co-morbid cirrhosis and chemo-resistance. Vaccination and improved treatment for hepatitis are the most effective means to reduce the burden of liver cancer worldwide. Expression of biomarkers such as AFP, DDK1 and microRNAs in blood are being tested for early screening of liver cancer. Since 2008, sorafenib has been used as standard molecular targeted agent for HCC. However, overall outcomes for sorafenib alone or in combination with other tyrosine kinase inhibitors are unsatisfactory. Simultaneously or sequentially, addiction switches and compensatory pathway activation in HCC, induced by sorafenib treatment, may cause acquired resistance to sorafenib. FOXM1 and MTDH have been shown to be master regulators of different aspects of tumorigenesis, including angiogenesis, invasion, metastasis and drug resistance. Elevated expression of both FOXM1 and MTDH is known to be a consequence of both activating mutations in oncogenes such as PI3K, Ras, myc and loss of function mutations in tumor suppressor genes such as p53 and PTEN in various types of cancers including HCC. The role of FOXM1 and MTDH as potential prognostic markers as well as therapeutic targets in HCC will be discussed. In addition, microRNAs (miRNAs), endogenous small non-coding RNAs involved in the regulation of gene expression, are involved in HCC and interact with both FOXM1 and MTDH in several ways. Thus, altered expression of miRNAs in HCCs will also be discussed as potential tools for diagnosis, prognosis and therapy in HCC.
Keywords: Hepatocellular carcinoma (HCC), MTDH, FOXM1, miRNAs

Type of the paper: Review
Synergistic Anti-Cancer Activities Of Natural Substances in Human Hepatoma HepG2 Cells
Authors: Akiko Kojima-Yuasa 1, Xuedan Huang 2 and Isao Matsui-Yuasa 1
Affiliations: 1 Osaka City University 2 Kitasato University
Abstract: Natural products are excellent sources for the development of new medications for disease treatment. Recently we and another researchers have been suggested that the combined effect of natural products may improve the effect of treatment against the proliferation of cancer cells. In this review we will introduce the combination of natural substances showing the synergistic anti-cancer effect in human hepatoma HepG2 cells and provide new insight into the development of novel combination therapies against hepatocellular carcinoma.

Last update: 27 April 2015

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