Scientists identify protein's crucial role in resistance to breast cancer treatment

Scientists at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research in London have identified how some breast cancers may become resistant to hormone treatments like tamoxifen.

The study, published in the February issue of the scientific journal Cancer Cell, shows for the first time that a protein called CDK10 is able to control the development of tamoxifen resistance in hormone sensitive breast cancer and has potentially important implications in the treatment of women with this form of the disease.

It is estimated that around 75% of breast tumours are hormone sensitive and use the female hormone oestrogen to grow. Tamoxifen and other anti-oestrogen drugs are a key treatment for women with this type of breast cancer because it reduces the ability of breast cancer cells to use oestrogen to grow, helping to prevent the disease spreading to other parts of the body or returning, and controlling tumours that have already spread. Tamoxifen can work extremely well for many women and has had a major impact on breast cancer survival. However, over time some patients’ tumours become resistant to tamoxifen.

Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre, says; “Some hormone sensitive breast cancers will eventually become resistant to tamoxifen and this is the major reason why cancer may return. Research to understand why this happens is vital if we are to develop ways to overcome it for the benefit of patients.”

To develop a better understanding of how this might occur, Professor Ashworth, Dr Christopher Lord and colleagues at the Breakthrough Breast Cancer Research Centre used a sophisticated screening method to identify genes that, when suppressed, cause tamoxifen resistance. The researchers identified Cyclin-Dependent Kinase 10 (CDK10) as a critical component in determining cancer cells’ response to tamoxifen and other hormone therapies.

Importantly, the researchers also found that patients with low levels of CDK10 in their tumours were less likely to benefit from tamoxifen treatment – their cancers were more likely to return, and they tended not to survive for as long as women whose tumours produced higher levels of the molecule. They also uncovered important information on how this might occur – showing that a process called methylation may to be critical to ‘switching off’ CDK10 levels inside breast cancer cells.

Professor Alan Ashworth adds; “Drug resistance is a serious problem for women with breast cancer. It’s devastating for a patient to see their cancer return because of resistance, especially after enduring a long course of treatment and after a long period of remission. Through this work, we’ve identified some of the factors that control this effect and in the future we may be able to use this information to decide which treatments to give to patients to avoid resistance.”

This research is just one example of the groundbreaking work taking place at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, Europe’s leading cancer research centre. One area of the centre’s work is to identify genetic changes that take place in breast cancer cells and use this knowledge to benefit patients in the clinic

Breakthrough Breast Cancer needs to raise at least £25 million each year for the next three years to support its vital research, campaigning and education work.

http://www.breakthrough.org.uk