Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 28, 2017; 9(21): 907-920
Published online Jul 28, 2017. doi: 10.4254/wjh.v9.i21.907
Chemotherapy for hepatocellular carcinoma: The present and the future
Marco Le Grazie, Maria Rosa Biagini, Mirko Tarocchi, Simone Polvani, Andrea Galli
Marco Le Grazie, Maria Rosa Biagini, Mirko Tarocchi, Simone Polvani, Andrea Galli, Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: The authors declare no potential conflicts of interest or financial support.
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:
Correspondence to: Andrea Galli, MD, PhD, Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences “Mario Serio”, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Telephone: +39-55-2758115 Fax: +39-55-2758411
Received: April 12, 2017
Peer-review started: April 12, 2017
First decision: May 19, 2017
Revised: June 13, 2017
Accepted: June 30, 2017
Article in press: July 3, 2017
Published online: July 28, 2017

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it’s still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatin- and gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC.

Keywords: Hepatocellular carcinoma, Systemic therapy, Chemotherapy, Molecular targeted therapy, Cytotoxic therapy, Immunotherapy, Perspectives

Core tip: The aim of this review is to make a point on chemotherapeutic options for treatment of hepatocellular carcinoma (HCC) at advanced stage, the most frequent stage of presentation of this neoplasia, still characterized by an important mortality rate. By now, sorafenib is the only standard treatment, but other options were recently studied and will be soon available for clinicians and patients affected by HCC. The review can be divided in four sections: The first one regards molecular target therapy and are described sorafenib, its open issues, but also other drugs with similar targets that have been evaluated for treatment of HCC. The second and the third parts regard cytotoxic drugs and immunotherapy, respectively, which were evaluated in recent years as possible alternatives or adjuvant to Sorafenib. In the last part of the review, future perspectives are described, in particular for what concerns resistance mechanism of the neoplasia, delivery methods or biological enhancers for drugs already in use, new drugs that will be probably evaluated and molecular targets that could soon become eligible for target therapy hopefully leading to the development of personalized therapy.