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Screen Finds Genes That Boost Sensitivity to Chemotherapy

RNAi screen identifies genes critical for regulating tumor sensitivity to paclitaxel

THURSDAY, April 12 (HealthDay News) -- Researchers have identified a set of 87 genes that regulate the sensitivity of tumor cells to taxane-based chemotherapies like paclitaxel, according to a report in the April 12 issue of Nature. Silencing some genes makes cells 1000-fold more susceptible to chemotherapy.

Michael A. White, Ph.D., from the University of Texas Southwestern Medical Center at Dallas, and colleagues used a library of short interfering RNA molecules to individually "silence" most known genes in the human genome in a human lung cancer cell line and test the sensitivity of these cells to paclitaxel, a microtubule inhibitor. Stringent statistical methods were used to reduce the likelihood of false positives.

The investigators found that silencing some genes increased the sensitivity of the cells by 1000-fold lower than the standard dose required to achieve a response. Some of the genes identified, like proteasome and ATPase subunits, are already targets of current therapeutics. The response seemed to be specific to paclitaxel since the results were not as dramatic for other chemotherapy drugs including vinorelbine and gemcitabine.

"The results reveal major fulcrums of the autonomous response of cancer cells to abrogation of microtubule dynamics," the authors write. "The results also identify therapeutic targets for combinatorial chemotherapy and highlight a major contribution of cancer-associated anomalous gene expression patterns for support of mitotic progression in cancer cells."

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