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Novel therapeutic approach to combat liver cancer identified

December 10, 2011 - Washington

Researchers have found a novel therapeutic approach, which could be used to treat or even prevent liver cancer - the third-leading cause of cancer death worldwide.

Scientists at Dana-Farber Cancer Institute in the United States have identified a mechanism in mice that triggers inflammation in the liver and transforms normal cells into cancerous ones.

They demonstrated in a mouse model that a particular micro-RNA (miR-124) - a member of a recently discovered class of molecular regulators - could be harnessed to treat or even prevent the dreaded disease.

"In this study we are describing for the first time a micro-RNA that is able to prevent and treat liver cancer," Dimitrios Iliopoulos, of Dana-Farber's Department of Cancer Immunology and AIDS said.

Iliopoulos and his colleagues found that in mice given a carcinogenic chemical, DEN, liver cancer was initiated by the activation of a molecular circuit that sets up an inflammatory state in the cells, leading to cancer.

Once this inflammatory circuit is turned on even for a few days, it becomes permanent, sustaining its activity through a never-ending feedback loop - a "snowball effect," as Iliopoulos termed it.

According to the Dana-Farber team, one element of the circuit is a micro-RNA called miR-124.

The research team found that miR-124 and another key controller of the feedback circuit, HNF4a, showed reduced activity in the cancer cells.

Because HNF4a and miR-124 interact with each other, the scientists hypothesized that boosting activity of miR-124 might restore normal activity in HNF4a, halting the runaway inflammatory cycle and causing tumors to stop growing.

To test this notion they administered systemically miR-124 once a week for four weeks to mice that had developed liver cancer by exposure to DEN.

"We found that miR-124 suppressed more than 80 per cent of tumor growth and size by causing the cancer cells to self-destruct," the scientists wrote.

They further showed that giving miR-124 to mice exposed to DEN actually prevented the development of liver tumors.

The findings are being published on Dec 9 in the journal Cell.


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