Scientists identify molecular 'switch' key to solving tamoxifen resistance
Last Updated: Wednesday, November 12, 2008 | 6:23 PM ET
The Associated Press
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Scientists have pinpointed the molecular on-off switch the powerful drug tamoxifen uses to attack breast cancer and which prevents the drug from working in some women.
That discovery should eventually help doctors test for resistance to the drug, the chief treatment for breast cancers that are estrogen-driven, researchers said.
Tamoxifen doesn't work in about one-quarter to one-third of women who are treated with it.
A test for resistance based on the research, published in Thursday's edition of the journal Nature, is probably about five years away, said study co-author Jason Carroll, a cancer researcher at the Cambridge Research Institute in the United Kingdom.
"We can use this information to predict which patients will respond to tamoxifen and more importantly which ones won't," Carroll told reporters in a telephone briefing.
"More importantly, it gives us an idea of what we should be making drugs against."
Tamoxifen turns off a gene that causes tumours to grow, but sometimes it fails in a molecular tug-of-war with another protein, and that's when the drug doesn't work, Carroll said.
"If that switch fails, the tamoxifen fails," he said. "The switch is hidden in the background of the genome in the gene itself."
For tamoxifen to work properly, it has to block a gene called HER2, which it does by using the hidden control switch.
Another protein called Pax2 must keep the switch in the off position, but that appears to fail among women who develop resistance to tamoxifen, the researchers said.
About 40,500 women die each year of breast cancer in the United States, according to the American Cancer Society. An estimated 5,400 women will die from the disease this year in Canada.
With files from ReutersShare Tools
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