Project details

Researcher: Professor J Ross Chapman

Location: University of Oxford

Project cost: £249,875

The challenge

We still don’t know enough about why some changes in the BRCA1 gene lead to breast cancer. And we need to know more about how tumours with BRCA1 gene changes respond to treatments.

Drugs designed to get rid of breast cancer cells with changes in their BRCA genes are called PARP inhibitors.

But we need to understand why these drugs sometimes don't work, or eventually stop working. And learn about which breast cancers with BRCA1 gene changes become resistant to PARP inhibitors and why. This will help us find better ways to treat these kinds of breast cancers.

The science behind the project

Our cells are constantly repairing damage to their DNA. BRCA1 and BRCA2 genes play an important role in helping cells to do this. But an altered BRCA gene means that mistakes and damage in DNA aren’t always fixed. This allows DNA to change in less helpful ways, which causes an increased risk of breast or ovarian cancer.

Researchers have recently learned that a protein called shieldin is also responsible for DNA mistakes in breast cancer cells with altered BRCA1 gene. But we need to learn more about:

  • Shieldin’s role in DNA repair
  • How it contributes to breast cancer progression
  • What part shieldin plays in cancer’s resistance to PARP inhibitor drugs

Ross and his team at the University of Oxford have perfected a way to isolate large amounts of shieldin in the lab. They can then use powerful microscopes to magnify it by up to 100,000 times. This allows them to see the individual building blocks that form the protein.

This allows the team to map the parts of shieldin that interact with DNA, and the parts that interact with other proteins. It’ll help them understand how shieldin works and how it’s involved in repairing DNA. Ross also wants to see exactly what happens to DNA and shieldin when breast cancer cells with BRCA1 changes are treated with PARP inhibitors.

What difference will this project make?

This research will increase our understanding of how changes in the BRCA1 gene can lead to breast cancer. It could lead to the improvement of existing treatments as well as the development of new ones for people with breast cancer caused by an altered BRCA1 gene.

How many people could this project help?

This project could help thousands of people. Each year, about 55,000 people find out they have breast cancer. We know that inheriting an altered gene, usually BRCA1 or BRCA2, is the underlying cause for about 5 to 10% of breast cancers.