Investigating a new approach to prevent breast cancer recurrence

We've made incredible progress in the diagnosis and treatment of breast cancer. More people are recovering from the disease and living longer than ever, but for some people tumours can return.

And when they do, they have often spread to other organs and tissues, with bone being the most common site. Cancer cells are drawn to nutrient-rich bone tissue, where they can go to sleep and hibernate or 'lay dormant' for 5-10 years or more.

Professor Penelope Ottewell and her team at the University of Sheffield previously found that a protein called IL-1β is made by breast cancer cells that spread to the bone, but not by those that don’t. They found that switching off this protein prevents breast tumours from growing in bone, sending them to sleep. However, this is only effective when tumours are small, before they are clinically detectable.

In the body, IL-1β is naturally switched off by a second protein called IL-1Ra. Now, the researchers want to find out whether enabling bone cells to make IL-1Ra can prevent cancer growth at this site. And which bone cells should be targeted to make this protein.

To do this, the researchers will genetically alter human breast cancer cells to make them produce high or low amounts of proteins involved in IL-1β activity. They’ll then look at which cells in the bone breast cancer cells interact with when they first begin to grow. They'll also look at how these are affected by IL-1β in human bone tested in the lab. After this the team will genetically target relevant bone cells, enabling them to produce IL-1Ra. 

The team will study how effective the new treatment is at preventing the growth of breast cancer cells in human bone samples in the lab and in mice. These experiments will allow the team to check that the new gene therapy has no unexpected side effects and is still effective at preventing breast cancer growth. 

Importantly, the treatment is specifically designed so that it’s delivered directly to the site where dormant tumour cells live. And the treatment will only be activated if dormant tumour cells start to reawaken, and only when IL-1β levels start to increase. This new gene-therapy treatment plan has real potential to prevent relapse in the bone without causing damage anywhere else.

This project will lay the groundwork for gene therapy based treatments that can prevent dormant breast cancer cells in the bone from reactivating. Since bone can act as a 'reservoir' for these cells, keeping them dormant could also reduce recurrence in organs like the lungs, liver and brain. The team will also aim to find the ways which IL-1β controls dormancy. And they’ll explore if drugs targeting IL-1β should be further looked at and developed.

55,000 women and 400 men are diagnosed with breast cancer every year in the UK. And this project could help thousands of people.