Dr Simak Ali

Understanding breast cancer resistance to hormone treatments

Dr Simak Ali leads the Breast Cancer Research Group based at the Hammersmith Hospital. The team’s research focuses on understanding how and why some breast cancers become resistant to hormone treatments such as tamoxifen and anastrazole.

Around eight out of ten women who get breast cancer, get a form of the disease called ‘hormone-sensitive’ breast cancer. These cancers need the naturally produced hormone oestrogen to be able to grow. Because of this, scientists have developed drugs called 'anti-oestrogens' (e.g. tamoxifen), which block oestrogen from fuelling breast cancer growth, and 'aromatase inhibitors' which prevent oestrogen production by the body.

Cancer Research UK has been instrumental in evaluating the best ways to use these hormone treatments, which have been hugely successful at helping to cut death rates from the disease.

Despite this, some hormone-sensitive breast cancers can develop resistance to these drugs over time, which can allow the cancer to start growing again. Dr Ali’s team is studying a protein called the oestrogen receptor (ER). This is present in hormone-sensitive breast cancers and signals cells to grow when oestrogen is present. Tamoxifen works by stopping oestrogen latching onto to the ER protein.

The team is investigating how changes to the ER protein can lead to drug resistance. In particular, they are focusing on how the ER protein can sometimes become activated in the absence of oestrogen, which might explain how breast cancers become resistant. They have found that a process called 'phosphorylation' can modify the ER protein and permanently activate it.

They are also looking for other proteins in breast cancer cells which can help to activate the ER protein, and so contribute to resistance. Understanding how breast cancers can develop resistance to hormone treatment should allow scientists to overcome this problem, and save even more lives.