A team of Nottingham scientists will explore whether drugs that disrupt this mechanism could cause breast cancer cells to self-destruct as a result of toxic levels of acidity.

Tuesday 12 September 2017      Latest research Our research
Dr Alan McIntyre

Dr Alan McIntyre

A prominent Nottingham scientist has been awarded a grant worth more than £90,000 by Breast Cancer Now to investigate how breast cancer cells control their acidity to avoid cell death, allowing them to spread around the body.

When breast cancer spreads around the body – known as secondary breast cancer – it sadly becomes incurable. The majority of the 11,500 women who die as a result of breast cancer each year in the UK will have seen their cancers spread. Over 730 women are diagnosed with breast cancer each year in Nottinghamshire, and more than 180 women in the region die from the disease every year.1

Breast tumours often grow very rapidly, and lack an adequate blood supply to continue to fuel this growth. This means that there can be a shortage of oxygen in these breast cancer cells – known as ‘hypoxia’ – and tumours that are lacking in oxygen are often more aggressive, and are more likely to spread throughout the body. Cells that are oxygen-deficient also tend to be acidic, but if tumour cells become too acidic, it results in their death.

Dr Alan McIntyre, based at the University of Nottingham’s School of Medicine, has previously found that some breast cancer cells produce higher levels of proteins called sodium-driven bicarbonate transporters (NDBTs), which act as ‘acidity regulators’, helping to keep conditions neutral so that tumour cells can grow and survive.

Dr McIntyre’s previous study found that disrupting these transporters’ function can prevent their ability to keep the tumour cell environment neutral, causing cells to become more acidic, ultimately leading to cell death.

With Breast Cancer Now funding, Dr McIntyre will now lead a three year project to uncover the exact role of NDBTs in the spread of breast cancer, and whether drugs that block NDBTs could prevent and control the spread of the disease around the body.

His team will investigate whether reducing the production of NDBTs, or blocking them using drugs could reduce the extent to which breast cancer cells invade – both in cells grown in the lab, and in mice. They will also investigate NDBTs’ location in the cell, and whether they move to the ‘leading edge’ to help tumour cells metastasise around the body. Crucially, the team will examine how NDBTs interact with other key molecules that control acidity, in order to understand how these interactions contribute to migration and invasion of tumour cells.

Dr Alan McIntyre, Assistant Professor at the University of Nottingham’s School of Medicine, said:

“One way of tackling breast cancer is to target the adaptations that help breast cancer cells evade hazardous conditions, such as acidity. With this funding from Breast Cancer Now, we can now explore whether targeting NDBTs is an effective strategy to prevent breast cancer spreading, which could ultimately save lives.”

Rachel Leahy, Research Communications Officer at Breast Cancer Now, said:

“Dr McIntyre’s work will reveal how sodium-driven bicarbonate transporters contribute to the spread of breast cancer, and could unveil a novel drug target for stopping the disease spreading around the body and becoming incurable. By blocking breast cancer cells’ ability to maintain a favourable pH, we may be able to drive them to self-destruct as a result of high levels of acidity.

“Our ambition is that by 2050, everyone who develops breast cancer will live, and if we are to achieve this, we must find new ways to prevent aggressive breast cancer cells colonising other parts of the body. Dr McIntyre’s project could help bring us one step closer to preventing breast cancer deaths, and we’d like to thank our supporters across the region who continue to help make our world class research possible.”

1.Source of information: Local incidence and mortality survival statistics were provided on request by Public Health England, April 2017 – similar data are available from CancerData. Figures are based upon averages for 2012-2014.