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World J Gastroenterol. Nov 14, 2022; 28(42): 6034-6044
Published online Nov 14, 2022. doi: 10.3748/wjg.v28.i42.6034
Angiogenesis and immune checkpoint dual blockade: Opportunities and challenges for hepatocellular carcinoma therapy
Si-Qi Li, Yang Yang, Lin-Sen Ye
Si-Qi Li, Yang Yang, Lin-Sen Ye, Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Author contributions: Li SQ, Yang Y and Ye LS carried out the research for the manuscript and edited all drafts of the paper.
Supported by Guangdong Basic and Applied Basic Research Foundation, No. 2019A1515110654; the National Natural Science Foundation of China, No. 82103448; and China Organ Transplantation Development Foundation, No. YZLC-2021-003.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lin-Sen Ye, Doctor, MD, PhD, Doctor, Postdoc, Surgeon, Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. ye_linsen@163.com
Received: August 27, 2022
Peer-review started: August 27, 2022
First decision: September 30, 2022
Revised: October 6, 2022
Accepted: November 2, 2022
Article in press: November 2, 2022
Published online: November 14, 2022
Processing time: 74 Days and 19 Hours
Abstract

The disease burden related to hepatocellular carcinoma (HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the approval of immune checkpoint inhibitors (ICIs) has provided a new therapeutic strategy for HCC. It is noteworthy that the positive outcomes of the phase III clinical trial IMBrave150 [atezolizumab (anti-programmed cell death ligand 1 antibody) combined with bevacizumab (anti-vascular endothelial growth factor monoclonal antibody)], showed that overall survival and progression-free survival were significantly better with sorafenib. This combination therapy has become the new standard therapy for advanced HCC and has also attracted more attention in the treatment of HCC with anti-angiogenesis-immune combination therapy. Currently, the synergistic antitumor efficacy of this combination has been shown in many preclinical and clinical studies. In this review, we discuss the mechanism and clinical application of anti-angiogenics and immunotherapy in HCC, outline the relevant mechanism and rationality of the combined application of anti-angiogenics and ICIs, and point out the existing challenges of the combination therapy.

Keywords: Anti-angiogenesis; Immunotherapy; Combination therapy; Vascular endothelial growth factor; Immune checkpoint blockade; Hepatocellular carcinoma

Core Tip: Anti-angiogenesis combined with immunotherapy in hepatocellular carcinoma (HCC) has attracted extensive attention. Although the mechanism of these combinations is largely understood, the biomarkers for predicting treatment response are still lacking. Thus, we outline the relevant mechanism and rationality of the combined application of anti-angiogenics and immune checkpoint inhibitors, and further explore the biomarkers that are associated with treatment response, which are critical in studies of HCC.