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Resistance Is Futile

photo - Mengnan Zhang in lab

Georgia Tech Graduate Research Assistant Mengnan Zhang moves samples of pancreatic cancer cells into a flask for study. The research examines the role of microRNA molecules in controlling resistance to chemotherapy drugs. Photo: Rob Felt

By increasing the level of a specific microRNA (miRNA) molecule, researchers have restored chemotherapy sensitivity in vitro to a line of human pancreatic cancer cells that had developed resistance to a common treatment drug.

If the miRNA molecules can be delivered to cells in the human body, the technique might one day be used to battle the chemotherapy resistance that often develops during cancer treatment. A Georgia Tech research team identified the miRNA used in the research with a computer algorithm that compared the ability of different miRNAs to control the more than 500 genes that were up-regulated in drug-resistant cancer cells.

The study was reported May 27 in the Nature Publishing Group journal Cancer Gene Therapy.

“We were specifically interested in what role miRNAs might play in developing drug resistance in these cancer cells,” said John McDonald, a professor in Georgia Tech’s School of Biological Sciences and director of the Integrated Cancer Research Center. “By increasing the levels of the miRNA governing the suite of genes we identified, we increased the cells’ drug sensitivity back to what the baseline had been, essentially undoing the resistance. This would suggest that for patients developing chemotherapy resistance, we might one day be able to use miRNAs to restore the sensitivity of the cancer cells to the drugs.”

MicroRNAs are small non-coding molecules that function in RNA silencing and post-transcriptional regulation of gene expression. The miRNAs operate via base-pairing with complementary sequences within messenger RNA (mRNA) molecules, silencing the mRNA molecules that control the expression of certain proteins. — John Toon

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