Zhang CY, Yang M. Targeting tumor vascular endothelial cells for hepatocellular carcinoma treatment. World J Gastroenterol 2025; 31(29): 110114 [PMID: 40809931 DOI: 10.3748/wjg.v31.i29.110114]
Corresponding Author of This Article
Ming Yang, PhD, Assistant Professor, Department of Surgery, University of Connecticut, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United States. minyang@uchc.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
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/
World J Gastroenterol. Aug 7, 2025; 31(29): 110114 Published online Aug 7, 2025. doi: 10.3748/wjg.v31.i29.110114
Targeting tumor vascular endothelial cells for hepatocellular carcinoma treatment
Chun-Ye Zhang, Ming Yang
Chun-Ye Zhang, Bond Life Sciences Center, University of Missouri, Columbia, MO 65212, United States
Ming Yang, Department of Surgery, University of Connecticut, School of Medicine, Farmington, CT 06030, United States
Author contributions: Zhang CY and Yang M designed, wrote, revised, and finalized the manuscript.
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: Ming Yang, PhD, Assistant Professor, Department of Surgery, University of Connecticut, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United States. minyang@uchc.edu
Received: May 30, 2025 Revised: June 21, 2025 Accepted: July 9, 2025 Published online: August 7, 2025 Processing time: 68 Days and 7.5 Hours
Abstract
Liver cancer is the sixth most common cancer and the third leading cause of cancer death worldwide. The predominant type of primary liver cancer is hepatocellular carcinoma (HCC). Tumor vascular endothelial cells (VECs), a major component of cells in the microenvironment of HCC, play multifaceted roles in contributing to tumor angiogenesis, proliferation, and migration, as well as therapeutic resistance by attracting myeloid-derived suppressor cells and suppressing cytotoxic CD8 T cell differentiation and function. Recently, Wu et al reported that apatinib, an inhibitor of vascular endothelial growth factor receptor 2, can inhibit tumor VEC glycolysis by regulating phosphatidylinositol 3-kinase/protein kinase B/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 signaling pathway to suppress HCC progression. With great interest, this editorial paper aims to review the function and key molecular signaling pathways of tumor VECs in HCC initiation and progression and summarize potential treatment options in clinical trials.
Core Tip: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, without effective treatment strategies for unresectable HCC. Tumor vascular endothelial cells have distinct features and functions from liver sinusoidal endothelial cells, lining the interior layer of cancer vascular vessels, and they contribute to tumor angiogenesis, proliferation, migration, and therapeutic resistance. Targeting liver tumor vascular endothelial cell molecular signaling pathways in the promotion of liver fibrosis, immunosuppressive cell infiltration, angiogenesis, and secretion of pro-metastatic factors is a promising strategy for HCC therapy or as a synergistic treatment.
