Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are primary liver cancers, both represent a growing challenge for clinicians due to their increasing morbidity and mortality.
HCC is the sixth most common cancer in the world, with 630,000 new cases diagnosed each year [1
]. The clinical history of approximately 80% of HCC patients progresses from fibrosis, to cirrhosis and finally to cancer [2
]. The three main causes of HCC are HBV and HCV infections and alcohol-induced liver injury. Less frequent causes are some autoimmune and metabolic diseases (starting from non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)). An additional rarer cause of liver carcinogenesis, especially in African and Asian Countries, is represented by aflatoxin B1 (AFB) [4
]. The mechanisms by which these aetiologic factors may induce HCC involve a wide range of pathways and molecules, currently under study.
CCA arises as a malignant transformation of cholangiocytes, the epithelial cells lining the intra- and extrahepatic biliary epithelium. CCA is an aggressive disease, with increasing incidence in Western countries [5
]; currently approximately 6000 new cases of CCA are diagnosed in the United States each year [6
]. Diagnosis is often made when the disease is already in its late stages. The therapeutic options (medical or surgical) are limited, which results in a poor prognosis. The vast majority of the patients die within a few months from diagnosis [5
The pathophysiology of CCA is poorly understood. The known definite or probable risk factors [such as Primary Sclerosing Cholangitis, liver fluke infections, hepatolithiasis or chronic hepatitis C, cirrhosis and toxins) share the common feature of inducing chronic cholestasis and biliary and/or liver inflammation [5
]. Thus, the development of animal models for better understanding the aetiology of these deadly cancers is essential. Over the last years a broad number of in vivo
models of HCC and CCA have been developed. The studyof these models are providing a significant contribution to unveiling the pathophysiology of primary liver malignancies. These models are also fundamental tools to evaluate newly designed molecules to be tested as new potential therapeutic agents in a pre-clinical set.
Because of the short lifespan and breeding capacity, rodents are widely employed for cancer research. Rats (Rattus norvegicus) or mice (Mus musculus) have also been favourite models for studying both HCC and CCA development. Mice are widely used to define the role of genetic modification through the use of knock or transgenic models, also because these models are easier to be handle.
The purpose of this review is to describe the technical and experimental features of the most significant rodent models, highlighting similarities or differences between the corresponding human diseases. For clarity, animal models were given specific names, in order to facilitate interpretation by readers.