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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Aug 24, 2020; 11(8): 589-605
Published online Aug 24, 2020. doi: 10.5306/wjco.v11.i8.589
Novel molecular targets in hepatocellular carcinoma
Ariel Ka-Man Chow, Simon Wing-Lung Yau, Lui Ng
Ariel Ka-Man Chow, Simon Wing-Lung Yau, School of Nursing and Health Studies, The Open University of Hong Kong, Hong Kong, China
Lui Ng, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Author contributions: Chow AKM wrote the paper; Yau SWL and Ng L commented and proof read the paper.
Conflict-of-interest statement: The authors declare no conflicts of interest related to this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Lui Ng, PhD, Research Assistant Professor, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China. luing@hku.hk
Received: February 28, 2020
Peer-review started: February 28, 2020
First decision: April 25, 2020
Revised: June 4, 2020
Accepted: June 20, 2020
Article in press: June 20, 2020
Published online: August 24, 2020
Processing time: 174 Days and 10.7 Hours
Abstract

Globally, hepatocellular carcinoma (HCC) is a leading cause of cancer and cancer-related deaths. The therapeutic efficacy of locoregional and systemic treatment in patients with advanced HCC remains low, which results in a poor prognosis. The development of sorafenib for the treatment of HCC has resulted in a new era of molecular targeted therapy for this disease. However, the median overall survival was reported to be barely higher in the sorafenib treatment group than in the control group. Hence, in this review we describe the importance of developing more effective targeted therapies for the management of advanced HCC. Recent investigations of molecular signaling pathways in several cancers have provided some insights into developing molecular therapies that target critical members of these signaling pathways. Proteins involved in the Hedgehog and Notch signaling pathways, Polo-like kinase 1, arginine, histone deacetylases and Glypican-3 can be potential targets in the treatment of HCC. Monotherapy has limited therapeutic efficacy due to the development of inhibitory feedback mechanisms and induction of chemoresistance. Thus, emphasis is now on the development of personalized and combination molecular targeted therapies that can serve as ideal therapeutic strategies for improved management of HCC.

Keywords: Hepatocellular carcinoma; Prognosis; Arginine deprivation; Cancer stem cells; Glypican-3; Hedgehog signaling pathway; Histone deacetylases; Personalized medicine; Molecular targeted therapy; Notch signaling pathway; Polo-like kinase 1; Tumour-associated antigens

Core tip: Hepatocellular carcinoma (HCC) remains a critical concern worldwide due to the severity of disease outcome. The primary cause is the low efficacy of current therapeutic regimens available to treat advanced HCC. This review provides details on novel potentially vulnerable targets in the oncogenic signaling pathways associated with HCC development and progression, which should be targeted to develop molecular combination therapies to improve disease management. Moreover, the identification and establishment of novel biomarkers would complement this process in assisting timely management of the disease via powerful personalized drug regimens.