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Preclinical breast cancer finding could change tamoxifen use

Blocking gene switch may get around drug resistance
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A team of Australian and U.K.-based researchers has found a new transcription factor in preclinical studies and this could change how common breast cancer drugs such as tamoxifen and aromatase inhibitors are used.

Transcription factors regulate how genes are expressed--in other words, they switch genes on and off. This specific transcription factor, known (perhaps rather aptly for the tail end of the Christmas season) as ELF5, can change how a breast cancer cell reacts to the common drug tamoxifen. ELF5 can switch off the cell's sensitivity to estrogen early in its life cycle, transforming the tumor into a more aggressive type of cancer that is no longer sensitive to tamoxifen and other aromatase inhibitors. The results are published in PLoS Biology.

The researchers found that by targeting ELF5 and changing its levels in breast cancer cells, they could change the subtype of the cancer. This opens up the possibility of overcoming drug resistance by changing a hard-to-treat cancer to one that responds to well-known and easily available drugs once more through new small molecule or small interfering RNA (siRNA) agents.

This could also be a useful biomarker that could pick out the cancers that won't respond to tamoxifen and other linked drugs, helping to improve existing diagnostic, predictive and prognostic tests and supporting doctors in choosing the best drugs for each patient.

- read the press release
- see the paper

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