Researchers at the University of Rochester Medical Center’s James P. Wilmot Cancer Center have made significant strides in the study of a primary cancer of the liver– Intrahepatic Cholangiocarcinoma (IHCC), also called biliary tract cancer. Their work has been published online and in print editions of Cancer Research, the most frequently cited cancer journal in the world.
Aram Hezel, M.D., an assistant professor of Hematology/Oncology in the Department of Medicine at URMC, is the corresponding author of the study that examined the role of genes commonly mutated in human cancers and their role in the growth of Intrahepatic Cholangiocarcinoma, a form of bile duct cancer.
Hezel and fellow researchers from URMC and Massachusetts General Hospital /Harvard Medical School succeeded in developing the first genetically engineered mouse model of IHCC that they hope will provide a valuable, new tool in further research of this disease. A mouse model is important to researchers as it enables them to test dozens or even hundreds of potential treatments in mice in a short span of time, accelerating the discovery process.
The model Hezel and his team created incorporates two of the most common mutations in humans – activating mutations of Kras and deletion of p53 oncogenes. An oncogene is a modified gene that increases the malignancy of a tumor cell. Some oncogenes, usually involved in early stages of cancer development, increase the chance that a normal cell develops into a tumor cell, possibly resulting in cancer.
“This is a new model of a less common liver tumor that we have not yet had good ways to study,” Hezel said. This represents the first good model that can be used as a tool to try to better understand this disease.”
Liver Cancer Facts
Liver cancer, or hepatocellular carcinoma, is a disease in which malignant cells grow in the tissue of the liver, one of the largest organs in the body.
The liver is an essential organ that people cannot live without. It processes and stores many of the nutrients absorbed from the intestine, causes the secretion of bile that helps in the digestion of food, and produces some of the clotting factors that keep you from bleeding too much when cut or injured. The liver gets most of its supply of blood from the hepatic portal vein, which carries nutrient-rich blood from the intestines; the rest comes from the hepatic artery, which supplies the liver with blood that is rich in oxygen.
Because the liver is made up of several different types of cells, several types of tumors can form in the liver; some are cancerous and some are benign.
Roughly 75 percent of primary liver cancers begin in hepatocytes (liver cells). Hepatocellular carcinoma most commonly occurs in people whose livers have been damaged. This damage is usually caused by alcohol abuse, by chronic infection with the hepatitis B or hepatitis C virus, or cirrhosis, from food contaminants, or from metabolic diseases.
Intrahepatic Cholangiocarcinoma is a primary cancer of the liver. It is thought to arise from the bile ducts, a series of branching tubes within the liver that deliver bile (which is produced by the liver) to the gallbladder and small intestine. Bile breaks down fats found in foods and also helps the body get rid of waste material filtered out of the bloodstream by the liver.
What causes liver cancer?
There are several causes of liver cancer, but the most common of all would be the following:
Men are most likely to have liver cancer because of their lifestyle.
If you are suffering from hepatitis B for a long time.
If you are ingesting alcohol most of the time, and abusing one self.
If the person is suffering from damaged liver cells such as the Cirrhosis of the liver.
People who are suffering from diabetes.
People who are overweight or obese.
People who have a large amount of aflatoxins in the body.
People who have large amount of vinyl chloride and thorotrast.
People who are taking too much anabolic steroids.
People who have ingested too much arsenic chemical.
The disease is diagnosed in approximately 6,000 people per year, and its occurrence is rising at a rate that makes it among the fastest growing liver cancers, for reasons scientists have not yet been able to pinpoint. Some suspect that it may be due to doctors having better tests to diagnose this type of cancer more accurately. The tumors are typically very aggressive and highly prone to metastasis at an early stage, leading to poor prognosis. To date, many aspects of IHCC’s biology and genetic makeup, as well as its cells of origin, have eluded scientists.
The model provides a relevant foundation for further understanding of the earliest, precancerous stages of IHCC, a better understanding of the tumor biology, and for evaluating effective treatments. The group has found that chloroquine - a drug commonly used to treat malaria – has been effective in treating IHCC in the mouse model.