Using the immune system to boost the effectiveness of drugs called PARP inhibitors

Drugs designed to get rid of breast cancer cells with changes in their BRCA genes are called PARP inhibitors. They can work very well for some patients, but not always. Also, sometimes breast cancers can become resistant to PARP inhibitors.

This means it’s vital to develop ways for PARP inhibitors to work faster and more effectively, before cancer becomes resistant. So more people diagnosed with breast cancer can live and live well

Many of the ways that the body fights bacteria and viruses can also work against cancer cells. One example is a defence system inside our cells called the cGAS pathway.

Our body normally turns on the cGAS pathway when it detects the DNA of harmful bacteria or viruses.

When treating breast cancer with PARP inhibitors, the breast cancer’s DNA can trigger the cGAS pathway. This can activate an immune response against cancer. But we don’t know much about how it happens.

So Dr Christian Zierhut and his team at the Institute of Cancer Research, London are investigating how the cGAS pathway finds breast cancer DNA. And how we can use this same process to turn on the immune system to improve treatment.

The researchers are using cutting-edge microscopy techniques to film breast cancer cells being treated with PARP inhibitors in fine detail. They’re using computer analysis to identify exactly how PARP inhibitor treatment turns on the cGAS pathway in breast cancer cells.

They’re also working in the lab to find out which genes control the cGAS pathway during PARP inhibitor treatment. This could help them to come up with new strategies to boost the immune system’s effectiveness against breast cancer cells.

This project could lead to a new treatment combination that boosts the immune response during treatment with PARP inhibitors.

A combination like this could successfully treat tumours faster, before they become resistant to PARP inhibitors. It could also make PARP inhibitors effective for more people. This would mean more breast cancers are successfully treated.

This project could help thousands of people. Around 55,000 women are diagnosed with breast cancer every year in the UK. Around 5 to 10% of these cancers are caused by an altered gene, most commonly the BRCA1 and BRCA2 genes. And cancers caused by changes in BRCA1 and BRCA2 genes can be treated with PARP inhibitor drugs.