Abstract: 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


INTRODUCTION

Primary liver tumors are the 6th most commonly diagnosed cancers and the second most common cause of cancer deaths around the world.1 Hepatocellular carcinoma (HCC) accounts for about 90% of primary liver tumors with the highest disease burden in sub-Saharan Africa and Asia where Hepatitis B virus (HBV) infection is endemic.2 Most of these cases, especially in Asia and Africa, present at an advanced stage, typically beyond the capability of curative treatment. Greater than 70% of HCC is diagnosed at later stages, typically when unresectable. The main treatment options for unresectable HCC include loco-regional therapy with trans-arterial chemoembolization (TACE) or systemic therapy with agents such as Sorafenib.

Anti-angiogenic therapy is currently the recommended therapy for advanced stage disease given the highly vascular nature of HCC.3 We will focus our discussion on pathophysiological concepts of angiogenesis in HCC, and the role of imaging in the assessment of angiogenesis and monitoring the response to treatment of patients with HCC treated with anti-angiogenic therapy.

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