Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies
Authors:   Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China, Yao Changyu , Wu Shilun ,   Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China, Kong Jian ,   Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China, Sun Yiwen ,   Department of Pathology, Peking University People’s Hospital, Peking University, Beijing 100044, China, Bai Yannan ,   Department of Hepatobiliary Pancreatic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China, Zhu Ruhang ,   Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China, Li Zhuxin ,   Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China, Sun Wenbing ,   Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China, Zheng Lemin ,   The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Health Sciences Center, Peking University, Beijing 100083, China; Beijing Tiantan Hospital, China National Clinical Research Center of Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100050, China
Published: January 2023

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Angiogenesis, the process of formation of new blood vessels, is required for cancer cells to obtain nutrients and oxygen. HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth, progression, invasion, and metastasis. Current anti-angiogenic therapies target mainly tyrosine kinases, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR), and are considered effective strategies for HCC, particularly advanced HCC. However, because the survival benefits conferred by these anti-angiogenic therapies are modest, new anti-angiogenic targets must be identified. Several recent studies have determined the underlying molecular mechanisms, including pro-angiogenic factors secreted by HCC cells, the tumor microenvironment, and cancer stem cells. In this review, we summarize the roles of pro-angiogenic factors; the involvement of endothelial cells, hepatic stellate cells, tumor-associated macrophages, and tumor-associated neutrophils present in the tumor microenvironment; and the regulatory influence of cancer stem cells on angiogenesis in HCC. Furthermore, we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC. A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.