Scientists at NUI Galway have discovered how cells related to one of the most aggressive forms of breast cancer can rewire themselves to have a better chance of surviving and spreading to other sites in the body.
The breakthrough finding by the team at the Apoptosis Research Centre in the University shows that a specific cell behaviour - known as the IRE1 stress response pathway - adapts the metabolism of triple negative breast cancer cells.
Afshin Samali, Professor of Cancer Biology and Director of the Apoptosis Research Centre at NUI Galway, said: “Most importantly, our research at NUI Galway shows that in fact this cell behaviour can be reversed through the use of specialised drugs inhibiting IRE1.”
The findings have been published in the internationally renowned Nature Communications journal.
The research focuses on cell behaviour in triple negative breast cancer, one of the most aggressive and difficult to treat forms of breast cancer. It accounts for about 15% of all breast cancers diagnosed and is more common in younger women.
Unlike other forms of breast cancer, there are no targeted therapies available for triple negative breast cancer.
Nutrient deprivation
The research highlighted how fast growing tumours often experience nutrient deprivation - meaning they lack what is required to grow and spread. However, cancer cells can rewire their metabolism - often referred to as metabolic reprogramming - to compensate for a low availability of nutrients.
The team at NUI Galway, led by Professor Afshin Samali and Professor Adrienne Gorman, demonstrate for the first time how the IRE1 stress response pathway rewires cancer cell metabolism. It does this by altering the levels of a key enzyme in lipid metabolism, which in turn increases the resistance of triple negative breast cancer cells to low nutrient conditions that often occur in the tumour.
The research also shows how this resistance can be reversed through targeted treatment.
Afshin Samali, Professor of Cancer Biology and Director of the Apoptosis Research Centre at NUI Galway, said: “The new era of precision oncology aims to tailor treatments to individual cancer patients. Here at NUI Galway, we have made a breakthrough and it is hugely exciting to identify new therapeutic target for triple negative breast cancer.
“Our previous research showed that inhibition of IRE1 improves the effectiveness of chemotherapy and reduces relapse of this highly aggressive form of breast cancer. Building on that, we can now demonstrate that this same cell pathway works to create an environment which makes it easier for these breast cancer cells to survive.
“What our research also shows is that targeting IRE1, or switching off the response mechanism of IRE1, could be particularly beneficial for the many patients whose cancer cells rely on the specific metabolic reprogramming it induces.”
Professor in Biochemistry, Adrienne Gorman, said: ‘We are getting ever closer to understanding the intricacies of cancer. Identifying new therapeutic targets such as IRE1 that are part of the tumour’s support system is very significant in offering another way to combat cancer.’
Dr Katarzyna Mnich, one of the research team at NUI Galway, said: “This work has uncovered a previously unknown role for IRE1 in triple negative breast cancer and it shows we need further investigation into the biology of IRE1. Most importantly for patients, the research also supports further development of IRE1 inhibitors as therapeutics for the treatment of triple negative breast cancer.”
The study was funded by Science Foundation Ireland and the EU under the Horizon 2020 programme.
