Project details

Researcher: Professor Andrew Tutt

Team: Target Validation and DNA Damage Response team

Location: Breast Cancer Now Research Unit, King's College London

The challenge

Triple negative breast cancer is one of the more aggressive forms of the disease and makes up about 15 per cent of diagnoses. Unfortunately, there aren’t many targeted treatments available for triple negative breast cancer. This means that treatment after surgery relies on chemotherapy and radiotherapy, which can have significant side effects.

What’s more, breast cancers can be resistant to treatments, meaning the treatment either doesn’t work at all, or stops working after a while once the cancer has learnt how to evade it.

We need to find new targeted treatments for triple negative breast cancer that can control the cancer effectively and permanently. It would ultimately save lives. Finding targeted treatments with fewer side effects would also help people with this form of breast cancer maintain a good quality of life.

The science behind the project

Professor Andrew Tutt and his research team at the Breast Cancer Now Research Unit in King’s College London want to change the way we treat triple negative breast cancer. He also leads a team at the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London.

Working with colleagues across the two sites, Andrew has found certain genes that are overly active in triple negative breast cancer. He now wants to understand their role in cancer cells. By revealing how these genes influence the disease, Andrew’s research can then be used to design kinder and smarter treatments. They would specifically target breast cancer cells, without damaging healthy cells, reducing the risk of side effects.

‘Much of our research is aimed at finding out the different ways cancer can evade new treatments and working out how to ‘get the upper hand again’. We’re aiming to develop more effective treatments for breast cancer that target tumour cells whilst leaving healthy cells unharmed. This would help to delay and even prevent the cancer coming back, and help to reduce the side effects associated with breast cancer treatment, so people can live well.’ - Professor Andrew Tutt

In parallel to work he’s leading at our Research Centre targeting breast cancers with changes in the BRCA1 and BRCA2 genes, Andrew and his team are  focusing on two projects at our Research Unit at King’s College London:

Studying a potential new drug target, GPR89

Research by Andrew’s team has discovered that a protein called GPR89 is often found at high levels in breast cancer cells. It also moves to a different part of the cell. The researchers also revealed a possible way in which it helps the tumour to grow. Now they want to find out how cancers with high levels of GPR89 might be targeted with drugs.

To do this, they want to better understand the role that GPR89 has in breast tumours. Andrew and his team will answer questions like: at what stage in tumour development does GPR89 become important; are certain types of triple negative breast cancers more dependent on GPR89 than others; and how does GPR89 interact with other proteins important for breast cancer growth and spread?

To do this, Andrew and his team are using samples of tissue from different stages of breast cancer donated by patients. They are also studying GPR89 by using genetic techniques to stop or limit GPR89 production, in mice with breast cancer and in 3D mini-tumours grown in the lab.

Creating ways to study breast cancers in the lab using cells donated by patients

A big challenge in breast cancer research is that sometimes promising discoveries made in the lab don’t work when they reach patients in clinical trials. There are many methods scientists use to study breast cancer which try to mimic the disease as it behaves in people, from cells grown in the lab to breast tumours in mice. Picking the right research method gives a greater chance of lab discoveries making a difference to patients.

In this project, Andrew and his colleagues are developing new methods to study breast cancer in the lab to support the research into kinder and smarter treatments.

They are using samples of tumours donated by patients being treated at the Royal Marsden Hospital and Guy’s Hospital. These samples will be used in different ways: some will be grown in the lab as 3D mini-tumours, and others will be used to develop mouse models of breast cancer.

They will represent different types of breast cancer, at different stages of the disease. Some of the samples will come from people whose cancer has already become resistant to certain treatments, which will allow the team to test ways to reverse or get around this resistance. They also hope to use samples with different genetic changes (such as BRCA gene mutations), and ones which overproduce or turn on proteins such as GPR89. Such changes can make breast cancer more aggressive, but they could be targeted with new treatments.

This work will enable all Breast Cancer Now-funded research teams at King’s College London and The Institute of Cancer Research to study and better understand the disease.

What difference will this project make?

As both a researcher and a clinician, Andrew is in an excellent position to translate his laboratory findings to benefit breast cancer patients. The work he is doing at our Research Unit at King’s College London and our Research Centre at The Institute of Cancer Research is focused on finding better treatments for triple negative breast cancers. However, these findings could also bring new treatments to patients with other forms of breast cancer. The ultimate aim is to find kinder, more effective treatments that help people with breast cancer live well and improve their chances of survival.

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