Finding targeted therapies for breast cancers

Thanks to research, we’ve made huge progress in improving treatments available to people with breast cancer. And while treatments can be effective against many cancers, not all of the breast cancer cells within an individual tumour respond. 

If we can understand what makes some cancer cells resistant to treatment, we can try to stop it – and let more people benefit from the treatments available to them.

Tumours are made up of diverse cancer cells that have different features and molecular changes. This means that each cancer cell can behave and respond differently to treatment. 

Rachael wants to know why some breast cancer cells resist treatment while others don’t and how this can change over time. The team first look at the molecular make-up of each individual cell within breast cancers that are resistant to treatment. This allows a detailed view of which cancer cells could make the disease more aggressive. 

They can then look for weaknesses in these individual breast cancer cells – and use genetic techniques to test whether getting rid of the cells stops tumours becoming aggressive. This could lead to more targeted therapies, helping more people benefit from treatments.

Rachael and her team are focusing on 3 projects:

1. Improving immunotherapy to treat triple negative breast cancers
   
   Immunotherapies use the power of the immune system to destroy cancer cells. One type of immunotherapy, called immune checkpoint inhibitors, is effective in treating some triple negative breast cancers – a type of disease that can be more aggressive and has less targeted treatments. But some tumours resist the treatment. 
   
   Rachael wants to find ways to improve responses to this type of immunotherapy. And she thinks that changes that happen to make breast cancer cells adapt quickly and make the cancer cells resistant can be reversed.
   
   The team are studying samples from people with triple negative breast cancer who have had immune checkpoint inhibitor therapy, and mice with this type of the disease. They want to understand if changes in these quickly adapting resistant cancer cells can be controlled and targeted with drugs to overcome this resistance.
   
   
   
2. Finding more treatments to stop secondary breast cancer
   
   When breast cancer cells leave the breast and spread around the body, they can grow into secondary tumours. We call this secondary breast cancer and, while it can be treated, it’s currently incurable. So, we need to come up with better ways to stop breast cancer spreading.
   
   Changes in a gene called KMT2C can help triple negative breast cancer resist treatment and spread by allowing them to adapt quickly. And changes in a gene called SF3B1 can help oestrogen receptor (ER) positive breast cancer evade standard hormone therapies. The team will study mice with primary and secondary breast cancer to understand what changes and find new treatment options for these tumours.
   
   
3. Understanding secondary lobular breast cancers to find new drug targets
   
   Invasive lobular breast cancer makes up around 15% of all breast cancers. And they tend to be ER-positive. Sometimes, lobular breast cancers don’t respond as well to some treatments – so we need to find better ways to treat it. 
   
   Rachael is investigating why some lobular breast cancer cells spread while others don’t. To do this she will study samples from people with lobular breast cancer as well as mice. She hopes this could lead to new ways to prevent secondary lobular breast cancer. 
   
   This research is part of the Lobular Initiative at our research centre. It’s a collaborative project that aims to understand lobular breast cancer more and find better treatments for it. 
   

Rachael’s project will give a better understanding of individual breast cancer cells, and help us understand why some tumours resist treatments. It could lead to improved treatments, and could make sure that every person gets the right treatment for their breast cancer.

Thousands. Changes in the SF3B1 gene occur in 8% of ER-positive breast cancers – that’s around 3,520 people diagnosed each year in the UK. It could also help the 8,000 people diagnosed with triple negative breast cancer, and the 8,250 with lobular breast cancer, every year in the UK.