Project details

Researcher: Professor Axel Behrens

Team: Cancer stem cell team

Where: Breast Cancer Now Toby Robins Research Centre, London

The challenge

Not all cancer cells in a tumour are the same. Because of this, some of them may respond differently to treatment and become resistant to it. And a small number of cells within the tumour called cancer stem cells are behind this. They’re also responsible for many processes such as tumour growth, recurrence and cancer’s survival. If we can effectively target these cancer cells with treatments, we may be able to help more people to live with and beyond breast cancer.

The science behind the project

Professor Axel Behrens’s team found a rare type of cell in the breast tissue of mice. These cells developed into oestrogen receptor positive (ER-positive) breast cancer, but only when they experienced specific changes. The cells had a protein on their surface, called Lgr6, and that’s how researchers could tell them apart.

Breast tumours grew much slower in mice when these cells were not there. It suggests that the cells with the Lgr6 protein were cancer stem cells, and tumours need them to grow quickly and survive. Now, Axel’s team want to understand the significance of the Lgr6 protein, and whether it can be targeted with treatments.

“We want to find better ways to treat breast cancer, by targeting breast cancer stem cells. They’re causing the disease to resist treatment, come back and spread to other parts of the body, where it becomes incurable. We’re now studying breast cancer stem cells that make the Lgr6 protein to find ways of eliminating them in breast tumours.” – Professor Axel Behrens

Axel and his team are focusing on 3 areas:

1) Understanding the role of Lgr6 in breast cancer stem cells

 Axel’s team are isolating cancer stem cells that make the Lgr6 protein. Then they’ll compare them to cancer cells without the protein following chemotherapy. To understand the differences between these cells, the researchers measure which genes become switched on or off, as well as how proteins react. This will help them to work out which genes and proteins may be responsible for resistance to treatment.

2) Developing better ways to study ER-positive breast cancer

We still need better ways to study breast cancer in the lab. We need to use new models of the disease that reflect how breast cancer emerges and changes in people. One of these methods is using 3D mini tumours called organoids. These tumours are grown in the lab from cancer stem cells that closely mimic the cancer that they’re originally from.

Axel’s team will develop organoids using tissue samples taken from people with ER-positive breast cancer. The samples will be taken before and after chemotherapy. The researchers will be able to highlight differences between pre- and post-treated samples and show how some cells become resistant to treatment during therapy.

3) Targeting breast cancer stem cells

The ER-positive breast cancer organoids create a platform for testing a wide variety of drugs. Axel’s team will then be able to test multiple drugs against Lgr6-positive cancer stem cells at a relatively high throughput. The researchers can then look at how the stem cells react, and how they may become resistant to treatment. They’ll be able to identify vulnerabilities in the stem cells, and come up with different ways to target them.

What difference will this project make?

Axel hopes that this work will make a real difference for people who are diagnosed with ER-positive breast cancer. If we can identify the stem cells that make a cancer tumour resistant to treatment, we will then be able to target them. This could result in more effective treatments for this type of breast cancer.