Cambridge Research Institute (CRI) scientists have discovered the molecular basis of tamoxifen response in breast cancer cells, and the reason why some women can develop resistance to the treatment, according to a study published online in Nature (doi:10.1038/nature07483; published online 12 November 2008).

Tamoxifen helps prevent breast cancer coming back so is given to most women for five years after they are first diagnosed. However some women develop resistance to the drug over time, meaning that their cancer is more likely to reappear.

The authors have discovered the mechanism for how tamoxifen works. It switches off a breast cancer gene ErbB2 via a protein called Pax2, which acts to keep ErbB2 switched off. Tamoxifen resistance occurs when ErbB2 remains switched on.

Lead author and CRI group leader Jason Carroll said: "We knew that women developed resistance to tamoxifen but previously our understanding of why this occurred could be compared with trying to fix a broken car without knowing how the engine worked. Now we understand how all the engine parts operate and we can try to think about ways to make repairs."

Cancer Research UK's chief scientist Professor Sir David Lane said that the results would: "...allow us to identify new targets for drug development and who will need such treatments".

For the full press release and other Cancer Research UK news, see online news.

For more details on the research behind this paper, see the research profiles of Jason Carroll, and the Histopathology Core Facility.