Treating Liver Cancer With Mirror Molecules

New research demonstrates that it is possible to selectively target and block a particular microRNA that is critical in the progression of liver cancer. The discovery may offer a new therapy for this malignancy, which annually kills an estimated 549,000 people worldwide. The findings are published in the journal, Cancer Research.

Conducted by researchers at The Ohio State University Comprehensive Cancer Center, the animal study focused on microRNA-221 (miR-221), a molecule that is present at abnormally high numbers in cases of liver cancer.

To inhibit this problematic molecule, the researchers created a second molecule as a form of mirror image of the first. The mirror molecule is called an antisense oligonucleotide, and it selectively bound and inhibited the functions of miR-221 in human liver cancer cells transplanted into mice. The treatment was found to greatly extend the animals’ lives and boosted the activity of critical tumor-suppressor genes.

According to lead researcher, Thomas Schmittgen, “This study is significant because hepatocellular carcinoma, or liver cancer, generally has a poor prognosis, so we badly need new treatment strategies.”

For the purpose of the study, Schmittgen and his fellow researchers injected liver cancer cells labeled with the luminescent lighting-bug protein luciferase into the livers of mice. The researchers used bioluminescence imaging to track the growth of the tumor.

When the tumors reached a critical size, the researchers administered the molecule designed to block miR-221 to one group of animals; the other group received a control molecule

The researchers discovered three critical findings. First, half of the animals treated with antisense oligonucleotide were alive after 10 weeks compared to none from the control group. Second, the antisense oligonucleotide greatly reduced levels of miR-221 in tissue samples taken from both the tumor and the liver. Third, treatment using the antisense oligonucleotide caused a three-fold increase in the activity of three tumor-suppressor genes blocked by miR-221 in liver cancer.

Schmittgen concludes, “Overall, this study provides proof-of-principle for further development of microRNA-targeted therapies for hepatocellular carcinomas.”


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