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Potential new drug combination for ER-positive breast cancer

Our scientists have found a potential new way to treat secondary oestrogen receptor (ER) positive breast cancers that have become resistant to existing drugs.

Scientists funded by us have discovered a potential new drug combination for ER-positive breast cancer that’s become resistant to palbociclib and hormone therapy.

They found that adding a new drug called AZD4573 to these existing treatments helped overcome resistance and improved their effectiveness.

In the future, this research could lead to clinical trials and a new way to treat ER-positive breast cancer that’s spread.

Finding ways to overcome resistance

Around 80% of breast cancers are ER-positive. Secondary ER-positive breast cancer can be treated with hormone therapy and drugs called CDK4/6 inhibitors, such as palbociclib. But some breast cancers can become resistant to these treatments over time.

So, Professor Clare Isacke at the Breast Cancer Now Toby Robins Research Centre wanted to find a new way to treat these tumours.

Screening for new drugs

To do this, Clare and her team screened more than 360 drugs on ER-positive breast cancer cells in the lab. They found that a CDK9 inhibitor called AZD4573 worked well on cells that were resistant to palbociclib. AZD4573 is currently in clinical trials for blood cancers.

They then tested this new drug in combination with palbociclib and found that the 2 drugs worked well together. The combination of AZD4573 and palbociclib was more effective than each of the drugs on their own.

The researchers then tested AZD4573 in combination with palbociclib and hormone therapy in mice, and they found it shrunk their tumours. The mice had tumours that came from 2 people with secondary hormone therapy-resistant, palbociclib-resistant breast cancer.

A new treatment combination

The team hope that in the future, this drug combination could be a new way to treat secondary ER-positive breast cancer that’s become resistant to palbociclib and hormone therapy.

More research and clinical trials are needed to test how effective this combination would be for people with a breast cancer diagnosis. And they’re needed to check the side effects of this drug combination.

Dr Kotryna Temcinaite, head of research communications and engagement at Breast Cancer Now, said:

 “With an estimated 61,000 people living with secondary breast cancer in the UK, more research to understand and treat it is vital.

“Discoveries like this can form the building blocks for the breakthroughs of the future. And we hope that further research will help translate these findings into new treatment options for people with secondary ER-positive breast cancer.”


The study was was funded by Breast Cancer Now and the Wellcome Trust, and it has been published in the journal Cancer Research.

Learn more about the research we fund.

Research we fund

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