Drug resistance mystery solved

Scientists have uncovered an explanation for why some women develop resistance to the breast cancer drug tamoxifen, giving hope that researchers will be able to find live-saving solutions to the problem.

The highly effective drug, tamoxifen, which is given to most breast cancer patients for five years after diagnosis, prevents tumours being fuelled by the female sex hormone oestrogen.

Over time, however, some women develop resistance to the drug and experience a recurrence of cancer. Scientists have now, for the first time, discovered why this happens.

They identified a regulatory molecule, PAX2, that helps tamoxifen work by switching off a cancer-promoting gene. Raised levels of another molecule, AIB-2, were found in tamoxifen-resistant tumours, with a molecular “tug of war” taking place between the two.

If AIB-2 wins, the tumour becomes resistant to tamoxifen, the study, published in the journal Nature, found.

Study leader Dr Jason Carroll, from the Cambridge Research Institute, said: "Now we understand how all the engine parts operate and we can try to think about ways to make repairs."

Earlier this year, Breakthrough Breast Cancer-funded scientists discovered a protein called CDK10 which can also control the development of tamoxifen resistance.

Dr Alexis Willett from Breakthrough Breast Cancer says:

"Tamoxifen is a key treatment for many women with breast cancer but we know some will become resistant to treatment over time and this is a major reason why cancer may return.  This research gives us a better understanding of one of the ways resistance can occur and is an important step towards developing improved treatments for patients.  It’s vital that research continues into why resistance occurs and how to overcome it.”

Copyright © Press Association 2008