I want to understand why cancer resists treatment, and find better ways to predict which patients will respond to therapy

I work in rare and difficult-to-treat cancers, particularly gastrointestinal cancers such as pancreatic cancer, as well as uveal melanoma and metastatic HER2-positive breast cancer. I want to understand why cancer resists treatment and find better ways to predict which patients will respond to therapy.

Pancreatic cancer is a rare disease, however, it is associated with poor prognosis, with a 5-year overall survival of approx. 12% and its incidence is increasing. The major challenge is late diagnosis. By the time symptoms such as jaundice, back pain, weight loss or general illness appear, the cancer has usually spread, and surgery is no longer a viable option. It is often called the “silent killer” because there are no clear early warning signs at an early stage.

The tumour microenvironment also makes pancreatic cancer highly resistant to treatment. The tumour is surrounded by dense stromal tissue that makes it harder for drugs to reach the cancer effectively.  Combined with advanced disease at diagnosis, this contributes to intrinsic drug resistance. 

My lab develops patient-derived organoids, or “mini tumours in a dish”, which we grow from surgical or biopsy samples donated by patients. Using 96-well plates, we can test multiple drug combinations at scale on these mini-tumours. One benefit of organoid models is that they better reflect the structure and diversity of tumours compared to  traditional two-dimensional cell cultures, which lack structural complexity and three-dimensional organisation present in pancreatic cancer. Our research focuses on using patient-derived organoids to understand why treatments fail and to identify better therapeutic options.

To do this, in our most recent research publication, we created organoids that became resistant to a common chemotherapy drug called 5‑fluorouracil (5‑FU), which is widely used in pancreatic cancer treatment regimens. By studying these resistant “mini-tumours in a dish”, we found that a protein called fatty acid synthase, or FASN, plays an important role in helping cancer cells survive treatment. Interestingly, when we targeted FASN using existing drugs or a new light-activated therapy (generated by Prof Tia Keyes), we were able to make these resistant “mini-tumours” respond to treatment again. In other words, re-sensitise them to chemotherapy. Our work suggests that targeting FASN could be a new way to improve how well chemotherapy works. While more research is needed, this study shows how we can use advanced models in the lab to better understand cancer and develop smarter, more effective treatments for patients with pancreatic cancer.

In our breast cancer research, one of our most important findings came through collaboration with St. Vincent's University Hospital and Professor John Crown. We identified a group of patients with metastatic HER2-positive breast cancer who survived far longer than expected on anti-HER2 therapy and chemotherapy. We compared the genomic make-up of their tumours with patients who relapsed quickly despite having similar clinical characteristics.

We discovered changes in the centromeric regions located at the center of chromosomes. Patients who responded long-term appeared to have amplified centromeric regions. We are still investigating why this matters, but the implications could be significant. Detecting these amplifications may help us stratify patients more accurately and personalise treatment decisions.

Uveal melanoma, a rare eye tumour, has traditionally relied on key molecular and genetic factors to establish metastatic risk. However, clinical practice has shifted, as many patients are now treated with plaque radiotherapy rather than eye removal. As a result, tumour tissue is no longer available for detailed molecular and histopathology testing, limiting our ability to stratify patients based on risk. To address this, working with colleagues from DCU Life Sciences Institute (LSI), we are examining whether tumour-derived DNA can be detected in the aqueous fluid of the eye. If we can profile the tumour cells in the aqueous fluid , we may be able to non-invasively identify which patients are at high risk of metastasis and which can be safely monitored. This could spare some patients unnecessary surgery while allowing closer surveillance and treatment for those at higher risk of the disease spreading.

In parallel, there is a need for improved laboratory models that better reflect the biology of uveal melanoma, particularly the process that drives the metastatic spread to the liver. Therefore, we are developing more biologically representative models to understand disease progression and to identify effective therapies to prevent or treat metastatic disease. 

What motivates me most is the ability to explore the underlying biology of tumours and more importantly how that translates to patient outcomes. Having the freedom to investigate complex biological questions and contribute to clinically meaningful translational insights is incredibly rewarding. Alongside my research, I also teach and contribute to curriculum development, something which I enjoy immensely and  has also opened new opportunities for engagement and impact. I particularly value mentoring PhD students as they develop patient-focused, clinically translatable research questions. It is very rewarding to support them as they develop into independent researchers.

The work is deeply personal because we rely on patient samples donated with consent. These contributions come from real people and families. While our research may not directly benefit the donors themselves, we hope it will improve outcomes for future patients.

I am increasingly focused on making research more translatable through collaborations such as the AllCaN Pancreatic Cancer programme, where I am a co-lead. These kinds of partnerships connect researchers with clinicians and patient representatives. The patients provide perspectives we would never see in the lab, including side effects that make treatments intolerable despite promising experimental results.

That patient perspective is essential. It makes sure our focus is not just on killing cancer cells in a dish, but on genuinely improving patient outcomes.