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Understanding how some triple negative breast cancers spread to other parts of the body

Research area: Secondary breast cancer

Dr Sankari Nagarajan is investigating how some triple negative breast cancers spread to other parts of the body. And she wants to see if drugs against proteins called nuclear receptors could stop this from happening.

What's the challenge?

Triple negative breast cancer is what we call breast cancer that is oestrogen receptor negative (ER-negative), progesterone receptor negative (PR-negative), and HER2 negative. This means that targeted treatments against these proteins don't work for triple negative breast cancers like they do for other types of breast cancer. So at the moment, triple negative breast cancer is mainly treated with surgery, radiotherapy and chemotherapy.

This type of breast cancer is also more likely to come back or spread in the first few years after treatment. When breast cancer spreads to other parts of the body, it’s called secondary breast cancer, and it’s currently incurable. Finding out exactly what makes triple negative tumours spread can help us develop new treatments.

The major hurdle in treating triple negative breast cancer is the fact that there aren’t many targeted treatments available. We’re still relying on chemo, which comes with gruelling side effects. If we can understand how these tumours invade other parts of the body, we can hopefully find new, better treatments. And ultimately improve survival and quality of life.

Dr Sankari Nagarajan

What's the science behind the project?

Dr Sankari Nagarajan leads a team of researchers at the University of Manchester. They recently discovered that lower levels of proteins called ARID2 and PBRM1 can help triple negative breast cancer cells spread.

Changes in ARID2 and PBRM1 proteins happen in different cancers, including triple negative. These changes can lead to lower rates of survival. The researchers investigated if other molecules are involved in this process, and found that ARID2 works with nuclear receptors. These receptors are present throughout the body and can control certain genes.

Sankari and her team are now investigating the exact ways in which ARID2 and nuclear receptors work together. They’re looking at how these proteins influence the activity of different genes in triple negative breast cancer cells. To do this, the team will use both cells grown in the lab and samples donated by people with triple negative breast cancer. Finally, the study will test some clinically approved drugs in mice, to see if they can control the spread of triple negative breast cancer.

What difference will this project make?

This project will help us better understand how secondary breast cancer develops. It could lead to new treatments for triple negative breast cancer that has changes in the ARID2 protein. Ultimately, this could improve survival rates and quality of life for people with this type of breast cancer.

How many people could this project help?

Thousands. Over 8,000 women are diagnosed with triple negative breast cancer each year in the UK – that’s around 15% of all diagnoses. And about a third of them will go on to develop secondary breast cancer. That’s why this research is so vital.

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