The Role of Angiogenesis in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers and is the second leading cause of cancer-related deaths worldwide. The hypervascular nature of most HCC tumors underlines the importance of angiogenesis in the pathobiology of these tumors. Several angiogenic pathways have been identified as being dysregulated in HCC, suggesting they may be involved in the development and pathogenesis of HCC. These data provide practical targets for systemic treatments such as those targeting the vascular endothelial growth factor receptor and its ligand. However, the clinical relevance of other more recently identified angiogenic pathways in HCC pathogenesis or treatment remains unclear. Research into molecular profiles and validation of prognostic or predictive biomarkers will be required to identify the patient subsets most likely to experience meaningful benefit from this important class of agents.

Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

“…Until recently, sorafenib, an oral, systemic, multikinase inhibitor, was the only approved treatment for advanced HCC and demonstrated a modest improvement in survival with an increased incidence of adverse events when compared with placebo . While several phase 3 studies of targeted therapies failed to show improvement over sorafenib in the first‐line setting, a few targeted therapies have recently been approved in different settings including lenvatinib in the first‐line setting, and regorafenib and cabozantinib following progression on first‐line therapy . Recent exploratory analyses suggest median overall survival (OS) of up to 26 months may be achieved with sequential treatments, but will require prospective studies to confirm.…”

“…Although there have initially been promising clinical results with immune checkpoint inhibitors, their role in this disease remains uncertain. Despite these advances, the current prognosis for advanced disease remains dismal with median OS ranging from 7.3 to 13.6 months, median progression‐free survival (PFS) from 3.1 to 7.4 months and objective response rates from 2% to 24% …”

Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression

“…Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and ranks the fourth cause of lethal tumor (Bray et al, 2018). HCC is a typical hypervascular tumor and commonly associated with hypervascularity (Srivastava et al, 2018;Morse et al, 2019). Therefore, inhibiting angiogenesis is believed to be a potential strategy to control HCC (Taketomi, 2016;Barbhuiya et al, 2017).…”

Targeting Receptor Tyrosine Kinase VEGFR-2 in Hepatocellular Cancer: Rational Design, Synthesis and Biological Evaluation of 1,2-Disubstituted Benzimidazoles

“…Hepatocellular adenocarcinoma (HCC) is regarded as one of the most life-threatening cancers around the world [29][30][31]. Recently, it was reported that overexpression of VEGFR-2 in HCC promotes pathological angiogenesis [32,33]. Hence, the application of VEGFR-2 inhibitors in HCC is considered one of the most successful approaches to hinder the growth and spread of hepatic cancer cells [33][34][35].…”