Potential New Treatment for Liver Cancer Discovered
BOSTON, MA--For the first time, researchers have discovered a special type of molecular regulator called a micro-RNA (miR-124) that could be used someday as a treatment for liver cancer. The same team also found a mechanism in mice that ultimately causes normal liver cells to transform into cancerous ones.
Liver cancer remains difficult to treat
Liver cancer will be diagnosed in an estimated 26,000 people in the United States in 2011, and nearly 20,000 individuals will die of the disease. Worldwide, liver cancer is the third cause of death caused by cancer, falling in behind lung (1.4 million deaths) and stomach cancer (740,000 deaths) at around 700,000 deaths.
Among the most common causes of and risk factors for liver cancer are chronic hepatitis B infection, which is common in Asia (where it is a childhood disease), hepatitis C (more common in Japan, Europe, and North America), alcohol abuse, and exposure to environmental toxins (including aflatoxin B1, which is the most potent liver cancer-causing chemical known), all of which can damage the liver and thus lead to cancer. Other factors include cirrhosis, hemochromatosis (disorder characterized by excess iron in the body), and non-alcoholic steatohepatitis.
In the new study, which was conducted by researchers at the Dana-Farber Cancer Institute, mice were exposed to a cancer-causing chemical called DEN, which triggered a circuit of inflammation in the liver that ultimately led to cancer. The investigators identified one element of the circuit called miR-124. Molecules in this class have been associated with different types of cancer.
Another key player in the circuit is HNF4α, a substance that has an important role in the formation of liver cells and their function. If HNF4α is suppressed, the result can be inflammation, which can then lead to cancer.
According to Dimitrios Iliopoulos, PhD, of Dana-Farber’s Department of Cancer Immunology and AIDS, he and the team decided to enhance the activity of miR-124 in hopes it would restore normal activity in HNF4α, which in turn would stop the inflammatory cycle and stop liver cancer from growing.
When they administered miR-124 to mice with liver cancer once a week for four weeks, they discovered that miR-124 halted more than 80 percent of liver tumor growth by causing the cancer cells to self-destruct. Another benefit of miR-124 was that it prevented the development of liver tumors.
Current treatments for liver cancer are limited. The only proven cure is a liver transplant. Individuals who have a small tumor may undergo a partial hepatic (liver) resection, although most people with liver cancer also have cirrhosis and cannot tolerate liver resection. Other treatments include chemotherapy, proton beam therapy, chemoembolization (delivery of chemotherapy directly to the tumor), radioembolization (a type of radiotherapy), and ablation, but the results are not promising at this point.
Iliopoulos and his team expressed the hope that “miR-124 potentially could be sued as a preventive in patients at high risk of liver cancer because they have chronic hepatitis C or as a therapeutic agent in patients with liver cancer.” The authors plan to begin a phase I clinical trial to explore this possible new liver cancer treatment in 2012.
Dana-Farber Cancer Institute
Picture credit: Wikimedia Commons