22 December 2021

Leading UK scientists funded by Breast Cancer Now and Cancer Research UK have discovered a way to significantly boost the effectiveness of xentuzumab, a new type of drug that has been tested a as treatment for breast cancer.

In this new study, researchers led by Dr Valentine Macaulay from the University of Oxford studied how blocking a protein called insulin-like growth factor (IGF) could be most effectively used against breast cancer.

In recent research published in the journal Cancer Research, the team discovered that blocking IGF delays the growth of breast cancer cells by slowing down the speed at which they can copy their DNA.

In this new paper published in Oncogene, the team explored how this finding can be exploited through new drug combinations, using the drug xentuzumab that has been trialed to treat people with oestrogen receptor positive (ER+) secondary (metastatic) breast cancer. The results of those recently completed trials are not yet known but will indicate whether IGF blocking drugs could be an emerging treatment for this form of breast cancer.

Xentuzumab blocks IGF in cancer cells, slowing down their growth and enhancing the effect of some anti-cancer treatments. But the impact that blocking IGF has on DNA copying was until now an unexplored cancer weakness.

The researchers treated breast cancer cells with xentuzumab together with a series of existing and emerging drugs that further interfere with DNA copying and DNA repair processes. Xentuzumab was most effective when combined with drugs MK-8776 and SRA737, which blocks a protein called CHK1, and AZD1775 that blocks the WEE1 protein.

The team discovered that when breast cancer cells are treated with xentuzumab and CHK1 or WEE1 blocker drugs, DNA copying stops almost completely. The result is catastrophic DNA damage that kills the cancer cells at a much higher rate, which could significantly improve the effect of the treatment.

It is hoped that these results could lead to a new effective treatment of IGF blocking drugs in combination with drugs that block CHK1 or WEE1, for people with ER+ secondary breast cancer.

Breast cancer is the most common cancer in women in the UK, with around 55,000 women and 370 men being diagnosed in the UK each year. Secondary (metastatic) breast cancer occurs when breast cancer cells spread away from the breast, through the blood and lymphatic systems to other parts of the body, and is at present incurable. It is not currently known exactly how many people have secondary breast cancer but it is estimated that 35,000 people in the UK are living with this devastating disease. Most of these cases will be ER+ and it is hoped this research will lead to new treatments for patients diagnosed with this type of breast cancer.

University of Oxford Scientists involved in the project include PhD student Xiaoning Wu and Breast Cancer Now funded Postdoctoral Scientist Dr Guillaume Rieunier.

Dr Valentine Macaulay at University of Oxford said:

“Before a cancer cell can divide into two cells it must make a complete copy of its DNA. Our recent research has shown that blocking IGF slows down the rate of DNA copying by reducing the supply of DNA building blocks. Our new discovery proves that we can exploit this finding to kill breast cancer cells more effectively. We hope these new findings will help to develop new combination treatments for people with breast cancer, by targeting processes that are essential for cancer cell growth."

Dr Simon Vincent, Director of Research, Support and Influencing at Breast Cancer Now, said:

“It’s estimated that 35,000 people in the UK are living with incurable secondary breast cancer, and most of these cases are likely to be oestrogen receptor positive.

“This new research provides important insight into the role of the IGF protein in the ability of cancer cells to copy their DNA and demonstrates how emerging drugs can be used to turn this process to our advantage. We hope these discoveries lead to urgently needed new and effective treatments that will stop people with incurable ER+ secondary breast cancer dying from this devastating disease.

“We’re proud to have funded this research, but due to the COVID-19 pandemic we’ve been less able to fund new research that could transform the lives of people affected by breast cancer. Your support is more critical than ever before. helping us to continue to bring hope for the future through our research. For more information and to donate visit breastcancernow.org/research.”