The Importance of Mouse Models in Liver Cancer Research
No human diseases have been cured without the assistance of animal research. Mouse models in particular have advanced pre-clinical studies and improved the outcome of a variety of serious medical conditions.
Liver cancer is one malignancy with a high mortality rate, but animal research has enhanced the health outcomes of patients with this disease. One paper published in the World Journal of Gastroenterology discussed how mouse models advanced liver cancer research over the years.
Liver cancer is the fifth most commonly diagnosed cancer in the world and the second leading cause of cancer death worldwide. In 2010, liver cancer resulted in an estimated 754,000 deaths worldwide, an increase of 64% from 460,000 in 1990, making it the third leading cause of cancer death worldwide after lung and stomach.
In the US, the American Cancer Society estimates that there will be 30,640 new cases of liver cancer in 2013, and 21,670 will die as a result. The majority of cases of liver cancer are secondary to infections with hepatitis B virus (45%) or hepatitis C virus (26%). An additional 20% of liver cancer cases are secondary to alcohol abuse.
Other external factors, like aflatoxin are also potent inducers of liver cancer. Due to these factors, 80% of the cases of the most common form of liver cancer, hepatocellular carcinoma, occur in sub-saharan Africa or east Asia, mirroring the incidence of hepatitis B. In the developed world, increasing rates of obesity and diabetes are now being linked to an increased risk of hepatocellular carcinoma. Hepatocellular carcinoma accounts for approximately 75% of all liver cancer.
Mice are some of the best models to use for studying liver cancer treatment due to their small size, similarities to human organs, and its entirely sequenced genome. There are three basic models of liver cancer in mice; implanted models, chemically induced models and genetic models.
In the implantation models, human liver cancer cell lines are implanted into immunodeficient mice, and the growth of the resulting tumors monitored, either by direct measurements, or through imaging systems. These models have the advantage of using human liver cancer material, but at the price of have to work in immunocompromised mice.
In the chemical models, susceptible strains of mice are treated with DEN (diethylnitrosamine), a genotoxic carcinogen, when they are between 12 to 15 days old. This causes liver tumors to appear in male mice at around 40 weeks of age.
Genetically-engineered mice expressing high levels of c-myc and TGF-a in their livers spontaneously develop liver cancer at very high rates by 40 weeks of age.
The long latency of both the chemically induced and genetically-engineered forms of cancer make mice good candidates for treatments designed to slow the progression of liver cancer, while the implantable models offer a more direct way of evaluating the capability of novel treatments to stop the growth and spread of existing cancer.
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Categories: Oncology