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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2016; 22(27): 6114-6126
Published online Jul 21, 2016. doi: 10.3748/wjg.v22.i27.6114
Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?
Liliana Montella, Giovannella Palmieri, Raffaele Addeo, Salvatore Del Prete
Liliana Montella, Raffaele Addeo, Salvatore Del Prete, Medical Oncology Unit, “San Giovanni di Dio” Hospital, Frattamaggiore, 80027 Naples, Italy
Giovannella Palmieri, Oncology Unit, Department of Clinical Medicine and Surgery, “Federico II” University of Naples, 80027 Naples, Italy
Author contributions: Montella L performed research and wrote the paper; Palmieri G, Addeo R and Del Prete S critically revised the paper.
Conflict-of-interest statement: No conflict of interest.
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: Liliana Montella, MD, Medical Oncology Unit, “San Giovanni di Dio” Hospital, via D.Pirozzi 66, Frattamaggiore, 80027 Naples, Italy. lilianamontella@libero.it
Telephone: +39-81-8891233 Fax: +39-81-8891333
Received: March 19, 2016
Peer-review started: March 22, 2016
First decision: April 14, 2016
Revised: May 9, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: July 21, 2016
Processing time: 118 Days and 15.3 Hours
Abstract

Cancer treatment has been revolutionized by the advent of new molecular targeted and immunotherapeutic agents. Identification of the role of tumor angiogenesis changed the understanding of many tumors. After the unsuccessful results with chemotherapy, sorafenib, by interfering with angiogenic pathways, has become pivotal in the treatment of hepatocellular carcinoma. Sorafenib is the only systemic treatment to show a modest but statistically significant survival benefit. All novel drugs and strategies for treatment of advanced hepatocellular carcinoma must be compared with the results obtained with sorafenib, but no new drug or drug combination has yet achieved better results. In our opinion, the efforts to impact the natural history of the disease will be directed not only to drug development but also to understanding the underlying liver disease (usually hepatitis B virus- or hepatitis C virus-related) and to interrupting the progression of cirrhosis. It will be important to define the role and amount of mutations in the complex pathogenesis of hepatocellular carcinoma and to better integrate locoregional and systemic therapies. It will be important also to optimize the therapeutic strategies with existing chemotherapeutic drugs and new targeted agents.

Keywords: Hepatocellular carcinoma; Targeted therapy; Pathway; Angiogenesis; Sorafenib

Core tip: Hepatocellular carcinoma (HCC) is a tumor with increasing incidence and epidemiologic relevance. Advanced hepatocellular carcinoma that is not amenable to radical treatments (i.e., transplantation or surgical resection) has a dismal prognosis (1-2 mo). Sorafenib, a tyrosine kinase inhibitor which targets multiple pro-angiogenic factors, is a cornerstone in the history of HCC treatments. Since the introduction of sorafenib, novel biological drugs have been investigated in hepatocellular carcinoma patients, but no monotherapy or combination therapy has significantly improved outcomes in clinical trials. Insights into tumor gene profile are critical in recognizing various classes of hepatocellular carcinoma in order to help determine which therapeutic approaches will be beneficial. Well-designed clinical trials may disclose differences in efficacy end-points, thus leading the way to clinical use.