Editorial
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
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: 67 Days and 23.2 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.

Keywords: Hepatocellular carcinoma; Vascular endothelial cells; Angiogenesis; Molecular signaling pathways; Therapy

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.