Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance

Liver cancer ranks as the sixth most prevalent malignancy globally, with Hepatocellular Carcinoma (HCC) constituting the predominant subtype, thereby imposing a significant burden on public health and presenting limited therapeutic options. Despite ongoing efforts to innovate treatment modalities, a...

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Main Authors: Hongtao Zhang, Zhaoming Yang, Zhengwu Jiang, Zhijian Zhao, Xun Chen, Jian Wan, Yukun Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1595195/full
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author Hongtao Zhang
Hongtao Zhang
Zhaoming Yang
Zhengwu Jiang
Zhijian Zhao
Xun Chen
Xun Chen
Jian Wan
Jian Wan
Yukun Li
author_facet Hongtao Zhang
Hongtao Zhang
Zhaoming Yang
Zhengwu Jiang
Zhijian Zhao
Xun Chen
Xun Chen
Jian Wan
Jian Wan
Yukun Li
author_sort Hongtao Zhang
collection DOAJ
description Liver cancer ranks as the sixth most prevalent malignancy globally, with Hepatocellular Carcinoma (HCC) constituting the predominant subtype, thereby imposing a significant burden on public health and presenting limited therapeutic options. Despite ongoing efforts to innovate treatment modalities, anti-angiogenesis therapy continues to be the primary strategy for managing HCC. Angiogenesis is a pivotal process within the tumor microenvironment, characterized by the formation of new blood vessels that provide essential nutrients and oxygen to proliferating tumors, thereby facilitating their growth and potential metastasis. Numerous angiogenic signaling pathways become dysregulated during this process. Targeting these aberrant pathways can yield significant therapeutic benefits for patients and may even reverse drug resistance. However, these signaling pathways frequently demonstrate intricate crosstalk and interconnections. Elucidating these interactions could represent a crucial strategy for advancing the treatment of HCC. This review provides both mechanistic insights into angiogenic network plasticity and translational strategies to overcome therapeutic bottlenecks in HCC management.
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id doaj-art-2c7aecf367594e66b4a513feb33d8e7d
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publisher Frontiers Media S.A.
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series Frontiers in Oncology
spelling doaj-art-2c7aecf367594e66b4a513feb33d8e7d2025-08-20T02:07:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15951951595195Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistanceHongtao Zhang0Hongtao Zhang1Zhaoming Yang2Zhengwu Jiang3Zhijian Zhao4Xun Chen5Xun Chen6Jian Wan7Jian Wan8Yukun Li9Jishou University Zhuzhou Clinical College, Medical College, Jishou University, Zhuzhou, Hunan, ChinaSecond Department of Hepatobiliary Pancreatic and Splenic Surgery, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, ChinaSecond Department of Hepatobiliary Pancreatic and Splenic Surgery, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, ChinaSecond Department of Hepatobiliary Pancreatic and Splenic Surgery, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, ChinaSecond Department of Hepatobiliary Pancreatic and Splenic Surgery, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, ChinaJishou University Zhuzhou Clinical College, Medical College, Jishou University, Zhuzhou, Hunan, ChinaSecond Department of Hepatobiliary Pancreatic and Splenic Surgery, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, ChinaJishou University Zhuzhou Clinical College, Medical College, Jishou University, Zhuzhou, Hunan, ChinaSecond Department of Hepatobiliary Pancreatic and Splenic Surgery, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, ChinaDepartment of Assisted Reproductive Center, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, ChinaLiver cancer ranks as the sixth most prevalent malignancy globally, with Hepatocellular Carcinoma (HCC) constituting the predominant subtype, thereby imposing a significant burden on public health and presenting limited therapeutic options. Despite ongoing efforts to innovate treatment modalities, anti-angiogenesis therapy continues to be the primary strategy for managing HCC. Angiogenesis is a pivotal process within the tumor microenvironment, characterized by the formation of new blood vessels that provide essential nutrients and oxygen to proliferating tumors, thereby facilitating their growth and potential metastasis. Numerous angiogenic signaling pathways become dysregulated during this process. Targeting these aberrant pathways can yield significant therapeutic benefits for patients and may even reverse drug resistance. However, these signaling pathways frequently demonstrate intricate crosstalk and interconnections. Elucidating these interactions could represent a crucial strategy for advancing the treatment of HCC. This review provides both mechanistic insights into angiogenic network plasticity and translational strategies to overcome therapeutic bottlenecks in HCC management.https://www.frontiersin.org/articles/10.3389/fonc.2025.1595195/fullhepatocellular carcinomaangiogenesisinhibitorpathwaysdrug resistance
spellingShingle Hongtao Zhang
Hongtao Zhang
Zhaoming Yang
Zhengwu Jiang
Zhijian Zhao
Xun Chen
Xun Chen
Jian Wan
Jian Wan
Yukun Li
Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance
Frontiers in Oncology
hepatocellular carcinoma
angiogenesis
inhibitor
pathways
drug resistance
title Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance
title_full Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance
title_fullStr Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance
title_full_unstemmed Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance
title_short Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance
title_sort aberrant angiogenic signaling in hcc therapeutic targeting and drug resistance
topic hepatocellular carcinoma
angiogenesis
inhibitor
pathways
drug resistance
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1595195/full
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