Researcher: Dr Jason Carroll
Location: University of Cambridge
Project title: Understanding the role of the gene ARID1A in the spread of oestrogen receptor positive (ER+) breast cancer
Up to 80% of breast cancers are oestrogen receptor positive (ER+) and are usually treated with hormone (endocrine) therapy, such as tamoxifen and fulvestrant. However, sometimes the breast cancer can become resistant to this treatment and can spread around the body. When breast cancer spreads, it can be treated but can’t be cured.
To support our 2050 aim that everyone diagnosed with breast cancer will live, we need research to understand what causes it to become resistant to treatments and find ways to prevent this from happening.
The science behind the project
Jason believes a gene called ARID1A plays an important role in how well hormone (endocrine) therapy works. Changes to the ARID1A gene that cause it to “switch-off” may make the breast cancer resistant to hormone therapy, and this could cause the breast cancer to spread around the body.
To investigate this, his team will use a new, state of the art model of oestrogen receptor positive breast cancer to recreate how breast cancer spreads around the body in mice. They will see how changes in the ARID1A gene influence the spread of breast cancer cells. Since ARID1A doesn’t work alone, researchers will also investigate what proteins it interacts with. This may uncover new ways to stop breast cancer spreading or to identify who is more likely to develop secondary breast cancer.
Jason and his team have also noticed that breast cancer cells with changes in the ARID1A gene are more susceptible to drugs called BET inhibitors. These drugs are currently in clinical trials to treat breast and other cancers. Researchers will also assess whether BET inhibitors could be used to treat secondary breast cancer with changes in the ARID1A gene.
What difference will this project make?
Understanding how the gene ARID1A is involved in breast cancer spreading could help find new ways to treat and prevent secondary breast cancer. This project will also help us understand if new drugs called BET inhibitors could be used to treat secondary breast cancer with changes in the ARID1A gene.
It could also reveal other proteins helping breast cancer spread that could be targeted with drugs or used to identify people at higher risk of breast cancer spreading so that they receive the most suitable treatment.
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