Project details

Researcher: Professor Kristijan Ramadan

Where: University of Oxford

Project title: Understanding the role a protein called SPRTN plays in breast cancer's resistance to PARP inhibitors

The challenge

PARP inhibitors are a type of targeted (biological) therapy. They can be used to treat secondary breast cancer. However, sometimes secondary breast cancer can become resistant to the PARP inhibitors. To support our objective is that by 2050 everyone diagnosed with breast cancer will live, we need to understand which breast cancers are more likely to become resistant to PARP inhibitors and what treatments can be used if this happens.

The science behind the project

PARP inhibitors are a type of targeted therapy that can be used to treat breast cancers with an altered BRCA1 or BRCA2 gene. These cancers rely on a protein called PARP to repair their DNA and keep growing. PARP inhibitors work by stopping this process and this stops the cancer growing.  

Professor Kristijan Ramadan and his team have been looking at how some breast cancers can become resistant to this treatment. Their early results show that a protein called SPRTN interacts with the PARP protein, helping it to become resistant to PARP inhibitors. This means the breast cancer could continue to grow and spread around the body.

To further understand the role that SPRTN plays in breast cancer’s resistance to PARP inhibitors, the team will experiment on breast cancer cells, specifically those with altered BRCA1 genes. They will use state of the art technology to look at the interaction between the SPRTN and PARP proteins and what happens when there is no SPRTN protein in a cancer cell. This will help to understand how the SPRTN protein helps some breast cancers to resist treatment with PARP inhibitors.

What difference will this project make?

Developing new treatments for breast cancers that have become resistant to PARP inhibitors will help to save lives. By understanding the role that the protein SPRTN plays in breast cancer becoming resistant to PARP inhibitors, this research could lead to new breast cancer treatments – such as treatments that target the SPRTN protein.  

Another possibility is by measuring the levels of SPRTN protein in breast cancer cells, healthcare professionals could in future predict how effective treatment using PARP inhibitors would be.

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