CANCER RESEARCH UK scientists have discovered the molecular basis for tamoxifen response in breast cancer cells - and the reason why some women can develop resistance to the treatment, according to a study published in Nature today (Wednesday).
Tamoxifen is given to most women for five years after they are first diagnosed with breast cancer to help prevent the disease from coming back but some women develop resistance to the treatment after time, meaning their cancer is more likely to return.
Researchers at the Cancer Research UK Cambridge Research Institute have discovered for the first time the mechanism by which the breast cancer therapy tamoxifen operates. It switches off a breast cancer gene ErbB2 via a protein called Pax2. Pax2 acts as a 'switch' to keep ErbB2 switched off. Tamoxifen resistance occurs when ErbB2 remains switched on.
Previously it was known that tamoxifen worked by blocking oestrogen from causing unchecked cell growth in breast cancer by switching certain genes on but the mechanism by which this occurred was unknown.
Lead author, Dr 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.
"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. 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."