Dr Clare Davies in the lab

Understanding how specific breast cancer cells resist chemotherapy

Research Area: Better treatments

Dr Clare Davies is investigating how a protein called PRMT5 can help triple negative breast cancer resist chemotherapy. This could lead to better treatment options.

What is the challenge?

Every breast cancer tumour contains a small number of special cells called breast cancer stem cells. They’re responsible for a tumour growing and progressing, as well as cancer’s resistance to treatments.

Specific proteins present within these stem cells are responsible for their resistance to DNA-damaging chemotherapy, one of these proteins is called PRMT5. Understanding exactly how these stem cells work is crucial to successfully treating breast cancer.

We’ll build on our recent discoveries to determine if the protein PRMT5 controls the production of other proteins in breast cancer stem cells that help them repair their DNA. We’ll use cutting-edge techniques to see how it affects cancer’s sensitivity to chemotherapy. This will give much-needed insight that could lead to the development of new treatments for breast cancer.

Dr Clare Davies

What's the science behind the project?

Dr Clare Davies of the University of Birmingham and colleagues are trying to understand what role a protein called PRMT5 plays in triple negative breast cancer.

Their recent discoveries show that PRMT5 helps breast cancer stem cells to repair their DNA. This means they can resist DNA-damaging chemotherapy that’s used to treat triple negative breast cancer.

Firstly, Clare’s studying specific changes in a process, which is essential for correctly making proteins, known as gene splicing. She’s measuring the effects of a drug that turns off PRMT5 to see if this then leads to gene splicing changes that increases cancer’s sensitivity to chemotherapy.

She’s also looking at how PRMT5 contributes to these splicing changes inside the breast cancer stem cells. Which could help researchers predict how well tumours and the breast cancer stem cell respond to these new treatments.

Lastly, she’s looking into a cutting-edge technology called antisense oligonucleotides (ASOs), which could treat triple negative breast cancer. ASOs can target specific genes that help breast cancer stem cells to repair their DNA. Clare also wants to know if this treatment can be combined with drugs that turn off PRMT5 and if this then makes cancer more responsive to chemotherapies. This could improve treatment outcomes for people with triple negative breast cancer.

What difference will this project make?

This project may tell us more about how some triple negative breast cancers resist chemotherapy. And give new treatment combinations for people with triple negative breast cancer.

It could also lead to brand new drugs to stop breast cancer becoming resistant to chemotherapy and other treatments.

How many people could this project help?

Thousands. Approximately 15% of breast cancers are triple negative. Over 8,000 women are diagnosed with triple negative breast cancer each year in the UK.

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