Harnessing the power of the immune system to treat breast cancer

There are 2 new types of treatment that have become available for some people with breast cancer in the last decade. Immunotherapies are treatments that use the power of the immune system to kill cancer cells. And drugs called PARP inhibitors, like olaparib, can be used to treat breast cancer with changes in BRCA genes. Both have been one of the biggest advances in breast cancer treatment in the last decade. But they don’t work for everyone. 

This is because some breast cancers can resist the treatments. And if we know how they do it, then we can find new ways to overcome this - allowing more people to benefit from these new treatments.

We now know that breast cancer cells can die in several different ways. And depending on how they die, they can release molecules that turn the immune system on or off.

When the breast cancer cells die in a way that turns the immune system on, it teaches the immune system to recognise and kill similar cancer cells. We call this immunogenic cell death. Pascal thinks it’s the key to destroying breast cancer cells that resist treatments. And it could offer long-lasting protection against the disease – this is because our immune system remembers what it destroys.

Pascal and his team are focusing on 3 main projects:

1. Combining immunotherapy with other drugs to improve responses
   
   One type of immunotherapy, called immune checkpoint inhibitors, is already used to treat some triple negative breast cancers. But it doesn’t work for everyone. 
   
   One of the ways breast tumours resist this therapy is by having overly active proteins called inhibitor of apoptosis proteins (IAPs). This stops breast cancer cells from dying.
   
   Pascal and his team want to test drugs to target IAPs. Then, they want to combine them with immunotherapy treatments. 
   
   The team is also developing new ways to improve the effectiveness of immunotherapies. They want to trick the immune system into thinking there’s an infection at the tumour site. This can direct the immune system to the tumour and help destroy more cancer cells. 
   
   
2. Developing a drug called RIPK1-PROTAC to treat breast cancer
   
   RIPK1 is a protein involved in many processes in healthy cells. But breast cancer cells can hijack it, so that they can hide from the immune system and prevent being killed. 
   
   The team use a pioneering technology called PROTAC (PROteolysis Targeting Chimeras) to target RIPK1. It uses the natural protein recycling system inside our cells. It labels a target protein, in this case RIPK1, to be broken down and recycled by the cell. 
   
   The team showed that their PROTAC drug diminished RIPK1 in breast cancer cells.  It also improved the effectiveness of immunotherapy and radiotherapy, when used together. 
   
   They’re now working to make it an effective new breast cancer drug. They’re improving the design of the drug so that it can be given as an injection into the blood stream. This could lead to the drug being taken to clinical trials.
   
   
3. Identifying ways to improve PARP inhibitors
   
   A PARP inhibitor drug, like olaparib, can be a life-saving breast cancer drug for some people with altered BRCA genes. But it’s not effective for everyone. Pascal thinks that he may be able to improve the effectiveness of PARP inhibitors by combining them with drugs that promote immunogenic cell death.
   
   The team are testing PARP inhibitors in combination with different drugs that do that, including their new RIPK1-PROTAC. 
   
   To do this, they’re collaborating with experts in the field - Professors Andrew Tutt and Chris Lord , who were key players in the initial PARP inhibitor studies and continue to focus on improving the effectiveness of these drugs.
   
   

By improving immunotherapies and PARP inhibitors, Pascal’s research could allow more people with breast cancer to benefit from these ground-breaking treatments – giving them more precious time.

Pascal’s research could lead to new treatments for the 8,000 people in the UK who are diagnosed with triple negative breast cancer each year. Triple negative breast cancer is more common in women who have inherited an altered BRCA gene. BRCA changed breast cancers impact around 1,375 people each year in the UK. And more than 40% of these breast cancers are resistant to PARP inhibitors.

While triple negative breast cancer is where the biggest unmet need is, Pascal’s research could help people with other types of breast cancer too. By creating new and innovative ways to treat breast cancer, his work could help the 55,000 women and 400 men that are diagnosed with breast cancer each year in the UK.