Supervisor View Full Details 2nd

• cancer/oncology

• Medicine
• Surgery
• Pathology

• Gastroenterology
• Oncology

The Centre for Cancer Research and Cell Biology (CCRCB) is increasingly recognised on the national and international stage for both its basic and translational research programmes in addition to its rapidly evolving clinical trial expertise. The CCRCB forms the hub of the Belfast Cancer Research UK (CRUK) Centre and provides a unique environment where researchers in basic science can work alongside and interact with clinical scientists in a variety of laboratory programmes. Our unifying research theme is to develop translational outputs, i.e. biomarkers and/or novel therapeutic strategies that enable CCRCB to be at the forefront of personalized cancer medicine.

The Upper Gastrointestinal Cancer Translational research group, led by Dr Richard Turkington, focuses on the application of knowledge generated by the analysis of genomic data to improving treatment selection and chemotherapy in pancreatic and oesophago-gastric cancer. As a clinically-led and focused group we work extensively with patient samples to test our research questions and advance our discoveries into clinical trials and interventions. We collaborate with a broad range of institutions nationally and internationally as well as multiple industrial partners. Our ultimate aim is to revolutionise the treatment of upper GI cancer in order to dramatically improve survival rates.

Identification of Targetable Mediators of Resistance to Chemotherapy in Oesophageal Adenocarcinoma

Background

The incidence of oesophageal adenocarcinoma (OAC) in men in the UK has risen 50% in the last 25 years. The five-year survival rate is less than 17% and even in early stage loco-regional confined disease this figure lies between 25-35%. There are pressing needs to identify biomarkers capable of predicting response to allow accurate treatment selection and to increase our understanding of the underlying mechanisms of chemotherapy resistance.

Materials

We have collected 300 FFPE pre-treatment endoscopic biopsy specimens from early stage OAC patients treated with cisplatin-based neo-adjuvant chemotherapy followed by surgical resection between 2004 and 2012 at 4 centres across the UK. Full clinical and response annotation are available for all cases, providing a unique dataset for biology discovery. A subgroup of 100 samples have matched fresh frozen (FF) tissue collected through the International Cancer Genome Consortium project (University of Cambridge).

Methodology

Transcriptional gene expression profiling (Almac Diagnostics Xcel array) and whole genome sequencing data are available for this patient cohort. We will discover the underlying biology of a resistance to chemotherapy in early stage OAC and pathway analysis of the microarray data will be carried out. We will identify pathways and genes governing histopathological response in early stage OAC to reveal novel drug targets, which will be extensively validated and subjected to mechanistic analysis. Promising drug targets will be taken forward in innovative early-phase clinical trials in combination with chemotherapy.

Conclusion

Through the application of our unique gene expression and sequencing dataset we will identify targetable mediators of drug resistance in early stage OAC and expand treatment options in this poor prognosis disease.