Project details

Researcher: Professor Chris Lord

Where: The Breast Cancer Now Toby Robins Research Centre, London

Team: Gene Function

The challenge

We’ve learned a lot about the molecular make-up of breast cancer. And it’s resulted in treatments that work very well for some people. But for others, these treatments don’t work, or stop working over time.

We need to explore weaknesses in breast cancer cells to develop kinder, smarter treatments that work for more people. So everyone can get the best possible treatment and their breast cancer won’t come back.

The science behind the project

Professor Chris Lord and his team are using cutting-edge laboratory techniques to look for new weaknesses in breast cancer cells.

New treatments targeting these weaknesses could be kinder and more effective, as they’ll leave healthy cells unharmed.

The team is also trying to understand why some breast cancers become resistant to treatments, and how to stop it.

“Many breast cancers respond well to treatment, but others don’t. If breast cancer doesn’t respond well to treatment, it’s likely to come back, spread, and eventually become incurable. So we want to stop people dying from breast cancer by improving the effectiveness of treatments.” – Professor Chris Lord

Chris and his team are focusing on 4 areas of research. On projects 3 and 4 they’re working closely with Professor Andrew Tutt, the director of our research centre.

1) Targeting changes in lobular breast cancer

Breast cancer that starts in the milk-producing glands (lobules) is called lobular breast cancer.

Lobular breast cancer cells often have changes to a gene called E-cadherin. Chris’s research has shown that changes to this gene make the cancer vulnerable to a lung cancer drug called crizotinib.

Now, Chris wants to understand which tumours with E-cadherin changes respond well to crizotinib and why. He’s working alongside Professor Nicholas Turner, using samples of breast cancer from the clinical trial ROLO.

Chris and his team are also researching ways that lobular breast cancer could become resistant to crizotinib. And looking for other weaknesses that could make lobular breast cancer vulnerable to new or existing drugs. They’re using breast cancer cells grown in the lab and mouse models of breast cancer.

2) Targeting changes in triple negative breast cancer

In triple negative breast cancer, there’s often a change to the gene Rb. Chris and his team have found that cancer cells with this change can be destroyed by blocking a specific protein called SKP2.

This makes SKP2 a potential new target for treatment. However, the SKP2 protein can’t be targeted with traditional drug molecules.

Traditional cancer drugs directly interact with the target protein to stop it from working. But Chris is exploring a new method. It takes advantage of the cell’s natural recycling system, by labelling the SKP2 protein for destruction by the cell. This treatment could be less susceptible to resistance and eventually be used to treat people with breast cancer.

3) Understanding how breast cancers with altered BRCA genes become resistant to treatment

The BRCA genes help to fix changes to our DNA.

When a BRCA gene is altered, cells aren’t as good at repairing DNA. This increases the risk of breast and other cancers. But it also makes breast cancer vulnerable to some chemotherapy drugs and PARP inhibitor drugs.

But breast cancer cells with altered BRCA genes can eventually become resistant to these treatments. And almost a third of them are resistant from the start.

Chris and his team want to overcome this resistance problem. They’ll look at samples of tumours donated by patients with altered BRCA1 or BRCA2 genes. And read the DNA of primary and secondary breast cancers that responded poorly or stopped responding to chemotherapy drugs (carboplatin), or PARP inhibitors.

4) Better understanding specific types of triple negative breast cancer

Some triple negative breast cancers make unusually high amounts of proteins called HORMAD1 and PUM3.

Chris and his team want to know why. They also want to understand how high levels of these proteins might help tumours to grow. And what weaknesses this could be causing in the tumours. The team hopes that high HORMAD1 or PUM3 levels might mean cancer is vulnerable to an existing or new treatment.

What difference will this project make?

This research is driving the development of new, kinder and smarter treatments for breast cancer. These treatments will target newly-found weaknesses in breast cancer cells.

If they work, these treatments will improve quality of life for people with breast cancer. And make sure the disease is treated successfully and doesn’t come back.

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