Bradford scientists awarded over £280k to develop new ultra-potent chemotherapy for breast cancer

Breast cancer remains the most common cancer in the UK. In West Yorkshire alone, more than 1,600 women are sadly diagnosed with breast cancer each year, and more than 350 women in the region die from the disease each year.¹

Chemotherapy is a cornerstone breast cancer treatment given to many patients to try to stop the disease spreading or coming back. With chemotherapy affecting healthy cells as well as cancer cells, many women and men experience debilitating side effects, such as hair loss, infections or anaemia. However, breast cancer cells can develop ways to resist chemotherapies, meaning treatment is not always successful.

Duocarmycins are some of the most potent natural compounds ever discovered – and it is thought that, if harnessed as a cancer treatment, they would be so powerful that tumours would not be able to develop resistance to them. However, as duocarmycins are so toxic, researchers need to find a way to deliver them to tumour cells whilst minimising damage to healthy cells and reducing any side effects.

With new funding from Breast Cancer Now – the UK’s largest breast cancer charity – two teams at the University of Bradford will explore different ways to unlock the potential of duocarmycins in treating breast cancer, ensuring they only become activated when they reach tumours. It is hoped that this could lead to a new, targeted treatment for all types of breast cancer, in particular, providing much-needed new options for those with aggressive disease, including ‘triple negative’ or metastatic breast cancers.

Dr Robert Falconer will lead a two-year project to develop new forms of duocarmycins that can remain inactive until they reach the tumour, passing through the bloodstream and tissues without damaging healthy cells. Dr Falconer’s team will test – in cells in the lab and in mice – the effectiveness of a variety of different ‘switches’ that can be activated by proteins that are only made by cancer cells, called MMPs (matrix metalloproteinases).

Dr Robert Falconer, Reader in Medicinal Chemistry at the University of Bradford, said:

“We are very excited by this opportunity to develop a new therapy for breast cancer. Duocarmycins are excellent anti-cancer molecules, but have proved simply too toxic for use in patients. Our approach will ultimately mean that these molecules can be turned into breast cancer drugs and safely given to patients, with their toxic effects limited to the tumour, where they will be specifically released.

“This Breast Cancer Now project award will enable us to lay the groundwork for our new therapy, and to ensure it is safe and effective in a lab setting. If all goes well, we’ll then be able to progress our best molecule into trials in breast cancer patients in the future.”

Dr Klaus Pors, also at the University of Bradford, has previously created a new form of duocarmycins that are activated by enzymes often overproduced by breast cancer cells, called CYPs (cytochromes P450). With Breast Cancer Now funding, Dr Pors’ team will now investigate whether these forms of duocarmycins can kill ‘triple negative’ breast cancer cells in the lab, and explore whether combining them with other anti-cancer drugs (that increase CYP levels, and therefore activate duocarmycins), or with radiotherapy, could make them even more effective.

Dr Klaus Pors, Senior Lecturer in Chemical Biology at the University of Bradford, said:

“Our research focuses on a family of enzymes called CYPs, which help protect our cells from harm. Some years ago we hypothesised that CYPs in cancer cells can be hijacked to activate duocarmycins, which we have now designed and developed.

“We have demonstrated that modified duocarmycins can be activated by CYPs in breast cancer cells, and we now need to investigate the potential of our technology in combination with other drugs and radiotherapy. We are very grateful to Breast Cancer Now for supporting our research over the next three years.”

Dr Simon Vincent, Director of Research at charity Breast Cancer Now, which is funding the research, said:

“This vital research in Bradford by Dr Falconer and Dr Pors could lead to a brand new, first-in-class form of chemotherapy, which we hope could one day benefit thousands of breast cancer patients.

“If it can be delivered safely, this powerful new chemotherapy option could help improve survival outcomes for women diagnosed with aggressive forms of breast cancer, who currently lack effective, targeted therapies.

“Side-effects of chemotherapy occur when drugs harm healthy cells, as well as killing tumour cells, and so if the teams at Bradford can develop new ways to target this new chemotherapy directly to breast tumours, many patients could be spared debilitating side-effects.

“Our ambition is that by 2050, everyone who develops breast cancer will live, and live well – and research is the key to achieving this. With the help of supporters across Yorkshire, we can fund more vital studies like this. It’s time to act.” 

Dedicated to funding the most cutting-edge research to stop the disease taking lives, Breast Cancer Now has so far invested over £200 million into world-class research. The charity is funding around a third of all breast cancer research happening in the UK, supporting nearly 380 leading scientists across the UK and Ireland.