‘A common misconception about breast cancer research is that it’s all been done’

27 Jan 2021

Dr Laura Barkley. Image: NUI Galway

NUI Galway’s Dr Laura Barkley explains how she is advancing breast cancer research to deliver more effective treatment for more patients.

Dr Laura Barkley of NUI Galway is the principal investigator of an Irish Research Council-funded collaboration to develop novel therapies for the treatment of breast cancer. This industry-academic collaboration between Barkley and Orbsen Therapeutics published a study last month in the International Journal of Cancer.

The research focuses on tumour stromal cells. An important component of solid tumours, stromal cells prevent the patient’s immune system from recognising and killing cancer cells and they also limit the effectiveness of many current cancer treatments, including immunotherapies. However, research from Barkley’s team indicates that developing drugs that specifically target tumour stromal cells may make currently available drugs more effective.

As the team works towards early clinical trials, Barkley explains this research and the avenues for treatment that it opens for cancer patients.

‘Research is important as we are continually trying to answer questions and come up with new and better ways to treat human disease’

What inspired you to become a researcher?

My A-level biology teacher, Ms Bradley, inspired me to become a researcher. I remember she set the class an assignment which encouraged us to make our own hypothesis and design experiments to test this hypothesis. I compared the sterility of still and sparkling bottled water. I got a real buzz from this and loved planning, executing my experiments and interpreting my results.

What research are you currently working on?

I have a strong interest and background in drug development and cancer biology. Initially, I did a pharmacology BSc in Manchester and a PhD in cancer biology at University College London, before taking up a FAMRI fellowship at Boston University. I have gained valuable experience working with major pharma companies including Glaxo and Zeneca.

During my career, while working in the UK, the US and Ireland, I have actively pursued opportunities which enabled me to study the interplay between cell cycle and other fundamental processes such as cell death, DNA damage checkpoints, DNA repair and differentiation. These opportunities have given me a strong understanding of how tumourigenesis [the process of tumour development] is impacted by multiple integrated pathways.

My current research is focused on examining the role of tumour stromal cells within the tumour microenvironment (TME). The tumour-associated stroma has received increasing attention for its role in initiating and sustaining tumour growth.

Tumour stromal cells secrete immunosuppressive factors that protect the tumour from attack by the immune system. I have established a multidisciplinary, collaborative research programme focused on examining the role of tumour-associated stromal cells and stromal cell-derived factors within the TME on tumourigenesis and chemoresistance.

Using patient-derived material and clinically relevant cancer models, these studies will unravel mechanisms of tumourigenesis and devise preventive and therapeutic measures that will positively impact cancer patient care.

In our recent publication, we discover that tumour stromal cells express a protein called syndecan-2 on their cell surface. We designed a novel drug to target this protein and show that this drug can block tumour growth and metastasis. One mechanism by which this drug inhibits tumourigenesis is by reducing the immunosuppressive niche caused by tumour stromal cells and allowing immune cells to attack the tumour.

In your opinion, why is your research important?

Research is important as we are continually trying to answer questions and come up with new and better ways to treat human disease. Take breast cancer, for example. In 1976 less than 50pc of women survived breast cancer over five years, whereas today 85pc of patients survive over this time period. This increase in survival can be attributed to research which has enabled early detection, personalised medicine (such as tamoxifen and Herceptin) as well as knowledge about causes and risk factors of breast cancer.

What commercial applications do you foresee for your research?

In the first instance, development of novel tumour stromal cell therapies (such as syndecan-2-biotherapeutics) as monotherapies in the treatment of cancer has significant commercial applications.

Additionally, we suggest tumour stromal-cell-based therapies will uncover the efficacy of current immunotherapies in breast cancer thereby opening up the multimillion-euro immunotherapeutic industry to otherwise unresponsive solid tumours.

What are some of the biggest challenges you face as a researcher?

The field of cancer biology is an exciting and continuously evolving area of research. This attracts a lot of top-class researchers to this field, making it very competitive. Therefore, one of the main challenges would be obtaining funding to carry out your research. However, the introduction of EU and national multidisciplinary consortium grants has helped cancer researchers to be involved in innovative projects with the potential of having real impact to patients.

Are there any common misconceptions about cancer biology research?

As mentioned above, there has been a significant improvement in the five-year survival of breast cancer patients over the years. Therefore, a common misconception about breast cancer research is that it has all been done. However, this does not take into consideration patients with triple negative, advanced metastatic or chemo-resistant breast cancer. There are limited treatment options for these types of breast cancer, therefore more research is required.

Tumour stromal cells have been shown to limit the efficacy of cancer therapies, contribute to metastasis and chemoresistance. Therefore, discovering a regimen to target tumour stromal cells is a key goal in breast cancer medicine.

Another way to address these misconceptions is through dialogue, especially from a young age. This is why I enjoy organising and participating in outreach programmes to local primary schools and charity events to discuss my research.

What research would you like to see tackled in future?

Tumour stromal cells are not unique to breast tumours. Therefore, I believe our research would be relevant and could be expanded to other stromal tumours such as pancreatic, lung and oesophageal.

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