Gastrointestinal Translational Research Programme
Obesity is a serious global health problem and is now estimated to be linked to 20% of cancer deaths and has the strongest association with oesophageal adenocarcinoma (OAC), of all malignancies. OAC has the fastest growing incidence of all cancers in Ireland and the increasing prevalence of obesity is thought to be one of the main contributing factors for this. The translational gastrointestinal team are examining the link between obesity and tumour immunity and modulation of the immune response. There are many strands to this including; the role of obesity on hepatic inflammation and post-operative recovery; the potential of novel chemokine receptor antagonists as an immunotherapeutic target for OAC through which tumour-specific T cell responses can be redirected away from the adipose tissue and liver and toward the tumour; elucidating the role of adaptive immunity in the progression of pre-malignant conditions and the role obesity plays in this setting is also examined.
In the context of the tumour microenvironment, the obesity programme also examines the connection between inflammation, hypoxia, angiogenesis and energy metabolism.
Response to cytotoxic and targeted therapies therapies in the neoadjuvant and adjuvant settings for GI patients is a significant clinical challenge. Being able to stratify which patients will and not respond to these treatments with high sensitivity and specificity will have significant impact. We continue to develop gene, microRNA and protein signatures with commercial potential as clinical tools.
As part of the thernanostic programme, we are developing novel small molecule inhibitors that can act as radiosensitisers in the neoadjuvant setting and as combinational therapies in the adjuvant setting with different licensed therapies. Many of our novel patented drugs have dual action: anti-angiogenic and anti-metabolic activity.
The effect of cytotoxic and targeted therapies on the tumour microenvironment and this crosstalk to the immune cells is a major focus in the programme. The effect of drug treatment can send signals to the dendritic and T cells to alter their response to reducing tumour burden, overall response to therapy and patient outcome. Using novel human explant work we examine in detail the connection between the response of the tumour to treatment and its connection with tumour immunity.
In collaboration with physiotherapists and nutritionist, we examine the role exercise and nutritional interventions play during the cancer patient’s journey from pre-neopastic GI diseases, through cancer treatment and during cancer survivorship.
The outputs of these translational themes in the multidisciplinary GI programme will benefit patient care, treatment and management for gastrointestinal diseased patients.