Abstract
Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, comprising approximately 80% of cases. Murine models of HCC, such as chemically-induced models, xenograft models, and genetically engineered mouse (GEM) models, are valuable tools to reproduce human HCC biopathology and biochemistry. These models can be used to identify potential biomarkers, evaluate potential novel therapeutic drugs in pre-clinical trials, and develop molecular target therapies. Considering molecular target therapies, a novel approach has been developed to create genetically engineered murine models for HCC, employing hydrodynamics-based transfection (HT). The HT method, coupled with the Sleeping Beauty transposon system or the CRISPR/Cas9 genome editing tool, has been used to rapidly and cost-effectively produce a variety of HCC models containing diverse oncogenes or inactivated tumor suppressor genes. The versatility of these models is expected to broaden our knowledge of the genetic mechanisms underlying human hepatocarcinogenesis, allowing the study of premalignant and malignant liver lesions and the evaluation of new therapeutic strategies. Here, we review recent advances in GEM models of HCC with an emphasis on new technologies.
Highlights
Liver cancer is a major health concern worldwide; it is the second leading cause of cancer-related deaths in East Asia and sub-Saharan Africa and the sixth in Western countries [1,2]
Mouse models for Hepatocellular carcinoma (HCC) have been developed through the introduction of genetic changes that contribute to the pathogenesis of the disease; with regard to the modeling of spontaneous HCC arising from a chronic inflammatory environment, there are considerable challenges that need to be overcome
This review aimed to provide a blueprint to understand the pathogenesis of HCC and optimize the preclinical models used in drug efficacy testing
Summary
Liver cancer is a major health concern worldwide; it is the second leading cause of cancer-related deaths in East Asia and sub-Saharan Africa and the sixth in Western countries [1,2]. Therapeutic options for patients with chronic liver disease and cirrhosis exist, such as potent antiviral therapies for hepatitis B and C, alcohol abstinence programs, and exercise routines for Cancers 2020, 12, 14; doi:10.3390/cancers12010014 www.mdpi.com/journal/cancers. Mouse models for HCC have been developed through the introduction of genetic changes that contribute to the pathogenesis of the disease; with regard to the modeling of spontaneous HCC arising from a chronic inflammatory environment, there are considerable challenges that need to be overcome. As it is becoming increasingly clear that there is no unique molecular pathway underlying the pathogenesis of HCC, various models are needed to mimic the different types of liver tumorigenesis. This review aimed to provide a blueprint to understand the pathogenesis of HCC and optimize the preclinical models used in drug efficacy testing
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