Angiogenesis in Hepatocellular Carcinoma; Pathophysiology, Targeted Therapy, and Role of Imaging

Abstract

Ahmed W Moawad,1 Janio Szklaruk,1 Chandana Lall,2 Katherine J Blair,1 Ahmed O Kaseb,3 Amita Kamath,4 Scott A Rohren,5 Khaled M Elsayes1 1Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA; 2Department of Radiology, University of Florida College of Medicine, Jacksonville, FL, USA; 3Department of Gastrointestinal Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA; 4Department of Radiology, Icahn School of Medicine at Mount Sinai West, New York, NY, USA; 5School of Medicine, Baylor College of Medicine, Houston, TX, USACorrespondence: Khaled M ElsayesDepartment of Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USATel [phone]Fax [phone]Email [email protected]: Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, usually occurring on a background of liver cirrhosis. HCC is a highly vascular tumor in which angiogenesis plays a major role in tumor growth and spread. Tumor-induced angiogenesis is usually related to a complex interplay between multiple factors and pathways, with vascular endothelial growth factor being a major player in angiogenesis. In the past decade, understanding of tumor-induced angiogenesis has led to the emergence of novel anti-angiogenic therapies, which act by reducing neo-angiogenesis, and improving patient survival. Currently, Sorafenib and Lenvatinib are being used as the first-line treatment for advanced unresectable HCC. However, a disadvantage of these agents is the presence of numerous side effects. A major challenge in the management of HCC patients being treated with anti-angiogenic therapy is effective monitoring of treatment response, which decides whether to continue treatment or to seek second-line treatment. Several criteria can be used to assess response to treatment, such as quantitative perfusion on cross-sectional imaging and novel/emerging MRI techniques, including a host of known and emerging biomarkers and radiogenomics. This review addresses the pathophysiology of angiogenesis in HCC, accurate imaging assessment of angiogenesis, monitoring effects of anti-angiogenic therapy to guide future treatment and assessing prognosis.Keywords: angiogenesis, hepatocellular carcinoma, anti-angiogenic therapy, Sorafenib

Keywords

• angiogenesis
• hepatocellular carcinoma
• anti-angiogenic therapy
• sorafenib