Hepatocellular Carcinoma Gene Study Unveils New Potential Drug Target


According to a study published in PLOS Genetics, a recent genetic study of hepatocellular carcinoma (HCC) cancer tumors has revealed vital information that could one day lead to a new and more effective treatment. With a poor survival rate, there is an urgent need to improve outcomes in this form of cancer. The researchers determined that a therapy targeting a gene called MAGEA3 could interfere in the tumor growth.

About Hepatocellular Carcinoma

Hepatocellular carcinoma is a type of liver cancer. Although generally considered rare, at least in developed countries, it is the most common type of cancer to originate in the liver in adults and is also the most common cause of death for people who develop cirrhosis. Risk factors are generally any condition that can lead to long term liver damage and cirrhosis, such as certain genetic disorders, chronic hepatitis, type 2 diabetes, nonalcoholic steatohepatitis, and severe alcohol abuse. The cancer is associated with common symptoms of liver dysfunction and damage, such as jaundice, fatigue, abdominal swelling, nausea and vomiting, bruising easily, abdominal pain, loss of appetite, and weight loss. Treatment may include kinase inhibitors, surgery, liver transplant, arterial catheters, and ablation. Survival rates are poor; cancer that cannot be removed with surgery is usually lethal within a year. To learn more about hepatocellular carcinoma, click here.

Research Findings

This research was led by a team from the Icahn School of Medicine at Mount Sinai. While previous studies have also revealed genes that drive tumor growth in this cancer, these discoveries have yet to translate into highly effective therapies. A total of 12 patients were involved in this study, with the research team collecting a total of 44 biopsies from their tumors. The scientists identified the high grade and low grade areas of the hepatocellular carcinoma tumors.

From this they used RNA sequencing in order to determine which genes were most highly expressed in the high grade regions. A group of genes called cancer testis antigens (CTAs) were frequently over-expressed in the most aggressive tumor regions. MAGEA3 was one example in this gene group that was closely linked to poorer outcomes, even more so than the entire CTA group as a whole. Under normal circumstances, CTAs are expressed in male germ cells, which are found in the testes. They are believed to both protect germ cells and contribute to the creation of sperm.

The team isolated individual cancer cells and blocked the expression of MAGEA3. They found that this caused the cells to stop growing, and they eventually died. In mice that were at risk of liver cancer, overexpressing this gene in the liver cells caused the animals to die from their cancer more rapidly. Further research will be needed in a larger samples to replicate these results and fully determine if inhibiting the MAGEA3 gene could be an effective therapeutic target.

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