By Leigh Parry
British scientists have discovered the mechanism that causes women to develop resistance to the breast cancer drug Tamoxifen.
Researchers at the Cancer Research UK Cambridge Research Institute found that tamoxifen works by switching off breast cancer gene ErbB2 via a protein called Pax2, they report in the journal Nature.
Pax2 acts as a ‘switch’ to keep ErbB2 switched off. Tamoxifen resistance occurs when ErbB2 remains switched off.
Lead author Dr Jason Carroll said scientists knew women developed tamoxifen resistance but did not understand the reasons why.
"We have discovered that for tamoxifen to work it has to block the gene ErbB2 and it does this by using a control switch that is hidden in the background of the genome, within the ErbB2 gene itself," he said.
"In order for tamoxifen to be effective, this switch must be held in the off position by Pax2. Now we understand how women can develop tamoxifen resistance."
Cancer Research UK’s chief scientist Professor Sir David Lane said the discovery would help identify new targets for drug development and who would need such treatments.
He said tamoxifen had been a "huge success story" in helping to prevent breast cancer recurrence.
Nature, November 12, 2008 doi:10.1038/nature07483
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