Synthetic RNA Blocks Tumor Formation in Cancer Model

A team of cancer researchers demonstrated that the synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC), could block the formation of liver tumors in a mouse model.

Liver cancer has emerged as the second most deadly malignant disease (more than 780,000 new cases and 740,000 deaths worldwide each year), with no efficient targeted or immune therapeutic agents yet available.

Investigators at the University of California, San Diego (USA) were working on the molecular mechanisms underlying the pathogenicity of liver cancer when they found that the synthetic dsRNA pIC, which is an immunostimulant that is used in the form of its sodium salt to simulate viral infections, significantly enhanced a variety of anti-tumor innate immune functions.

They reported in the November 14, 2017, online edition of the journal Cell Reports that injection of pIC at the pre-cancer stage robustly suppressed formation of liver tumors that had been induced either by chemical carcinogens or by Pten loss with associated fatty liver disease. The dsRNA inhibited liver cancer initiation, apparently by boosting multiple anti-tumor activities of innate immunity, including induction of immunoregulatory cytokines, activation of NK (natural killer) cells and dendritic cells, and reprogramming of macrophage polarization.

"The findings suggest that the drug may prevent liver cancer. We have more work to do, but we could make a real impact at a time when liver cancer rates are increasing," said senior author Dr. Gen-Sheng Feng, professor of pathology and molecular biology at the University of California, San Diego. "There is a large population living with chronic liver disease who are at high risk of developing cancer. If we can develop a vaccine that prevents tumor formation or a therapeutic combination that stops existing cancer from growing, we could reduce the rapid increase of liver cancer rates."

"The liver has unique immune tolerance, which is why existing treatments, including immunotherapy, have little to no lasting effects on liver cancer," said Dr. Feng. "We 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."

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