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Primary liver cancer is now the second leading cause of cancer-related death across the globe.In late stages of the malignancy, there are no effective treatments or drugs. While studying the pathogenic mechanisms of liver cancer, the researchers discovered that a commonly used synthetic double-stranded RNA dsRNA strongly boosts a variety of anti-tumor innate immune functions. They suggest it may have the potential to be administered as a vaccine to prevent cancer in individuals at high-risk of developing liver cancer.
The liver has unique immune tolerance, which is why existing treatments, including immunotherapy, have little to no lasting effects on liver cancer. Researchers were initially performing gene deletion to investigate how different types of cells communicate in the liver to promote or suppress cancer development when we found that this synthetic double-stranded RNA prevented liver cancer from initiating by harnessing the body’s own innate immune system.
Researchers describe how dsRNA polyinosinic-polycytidylic acid pIC prevented primary liver cancer from occurring in mouse models when it was injected into the body cavity during the pre-cancer stage. Primary liver cancer is cancer that begins in the liver; metastatic liver cancer starts elsewhere in the body and spreads to the liver. The study showed that the formation of tumors or tumorgenesis was suppressed by reprogramming macrophages -specialized immune cells that destroy targeted cells and activation of natural killer cells and dendritic cells that kill tumor cells directly or boost adaptive immunity.
Mouse models with tumors induced either by chemical carcinogen or fatty liver diseases were injected with pIC at different stages. Tumor inhibition was successful in all models that received the dsRNA before tumor formation. The greatest decrease in tumor numbers and size was seen when pIC was administered at one month. At three months the impact was reduced but still significant. At five months, when tumors had already began to form, there was little inhibitory effect observed when comparing tumor numbers or sizes to control groups. The findings suggest that the drug may prevent liver cancer. Liver cancer in adults is among the leading causes of cancer mortality in the world, with more than 780,000 new cases and 740,000 deaths each year.
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