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Gene Screening Points Way to More Effective Chemotherapy

Using a technology that can quickly screen all 20,000-plus human genes for biological activity, scientists have isolated 87 genes that seem to affect how sensitive human cancer cells are to certain chemotherapy drugs.//

In a study available online and appearing in the April 12 edition of the journal Nature, researchers at UT Southwestern Medical Center describe how they used a library of small RNA molecules – the first used by a university research center – to identify the genes.

When the researchers blocked the action of some of the 87 genes inside isolated lung-cancer cells, they found that those cells were up to 10,000 times more sensitive to the chemotherapy drug paclitaxel (Taxol).

The results are important because the ability to lower the dose of chemotherapy drugs without compromising effectiveness reduces debilitating side effects, said Dr. Michael White, professor of cell biology at UT Southwestern, associate director for basic science at the Simmons Comprehensive Cancer Center, and senior author of the study.

“Chemotherapy is a very blunt instrument,” he said. “It makes people sick, and its effects are very inconsistent. Identifying genes that make chemotherapy drugs more potent at lower doses is a first step toward alleviating these effects in patients.”

The current study tested only isolated cancer cells, so further studies will be needed to determine whether blocking the genes in living animals has the same effect.

The findings were made possible because of a technology that allows scientists to rapidly test how cells react when a given gene is turned off, or “silenced.” The so-called high-throughput employs a series of small plastic dishes, each with 96 wells. Using a robot, researchers place small bits of RNA that can block the function of one gene into each well on the plate. Next, non-small-cell lung cancer cells are placed in each well with the RNA.

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