In a world first, NUI Galway researchers have identified a treatment strategy for the relapse of an aggressive form of breast cancer.
Scientists from the college’s Apoptosis Research Centre published their findings in the journal Nature Communications today after months of research.
The treatment – which involves targeting a specific stress response pathway called IRE1 – may improve patients’ response to chemotherapy and reduce relapse rates for patients with triple negative breast cancer.
Triple negative breast cancer (TNBC) is one of the most aggressive and difficult to treat forms of breast cancer.
It accounts for around 15% of all diagnosed breast cancers and occurs more often in younger women.
There are currently no targeted therapies available for TNBC.
Chemotherapy is the main treatment – but a large percentage of TNBC patients relapse within one to three years and have a poor long-term prognosis.
Director of the Apoptosis Research Centre Professor Afshin Samali led the NUIG research team that discovered the mechanism for cancer relapse after chemotherapy.
Cellular stress sensor IRE1 normally acts to alleviate short-term stresses within cells, such as lack of nutrients or oxygen.
It is a central driver of treatment-related relapse.
Professor Samali commented: “Here at NUI Galway, we are excited to identify a new therapeutic strategy for triple negative breast cancer patients who are most in need of better treatment options. Furthermore, this strategy may benefit many other cancer patients whose cancer cells rely on activated cell stress responses to survive.”
First author of the study Dr Susan Logue said: “This work has uncovered a previously unknown role for IRE1 and suggests that it may represent a good therapeutic target for the treatment of triple negative breast cancer.
“While further research is needed, this work is a great example of how curiosity-driven basic research can lead to translational outcomes with real potential to impact on patient treatment.”
The team discovered that chemotherapy can activate the IRE1 stress response in TNBC – leading to the production of survival signals that support the growth of new cancer cells.
This process can be stopped by inhibiting IRE1 using a small molecule drug called MCK8866 that not only improves the effectiveness of the initial chemotherapy treatment, but also reduces the chance of relapse.
Using cancer cells treated with chemotherapy, the research team found that blocking IRE1 decreased survival signals and reduced the growth of new cancer cells by 50%.
The drug also increased the effectiveness of chemotherapy treatment, leading to regression of 8 out of 10 cancers compared to regression of just 3 out of 10 cancers using chemotherapy alone.
The combination of the MCK8866 drug with chemotherapy also reduced tumour relapse in a pre-clinical model of triple negative breast cancer.
Alongside the laboratory experiments, an analysis of 595 real tumours showed that TNBC tumours displayed the highest IRE1 activity compared to other subtypes, suggesting that IRE1 may be of particular importance in this aggressive type of cancer.
This discovery suggests that combining chemotherapy with IRE1 inhibitors could offer substantial benefits for triple negative breast cancer patients.
The study was funded by Science Foundation Ireland, Irish Cancer Society and Horizon 2020 with initial funding from Breast Cancer Now.
