My main research themes relate to resistance to cancer therapies and stratified medicine including the development of clinical trials to
investigate the clinical and cost-effectiveness of both new and existing treatments. I am part of the QUB Centre for Cancer Research and Cell Biology (CCRCB) Drug Resistance Group working particularly with Prof D Longley, and also with Prof M Salto-Tellez, in translational research that focuses on potential biomarkers and mechanisms of resistance to commonly used anti-cancer therapies, in particular the role of the immune response in resistance to treatment and immunogenic cell death.
Acquisition of drug resistance may occur as a function of genomic instability of tumour cells, facilitating their ability to adapt to the damage induced by DNA repair by cellular and molecular alterations including activation of pathways to avoid apoptosis. CCRCB has a long established focus on using genomic profiling of in vitro models and cohorts of colorectal cancer tumour specimens to identify biomarkers associated with treatment response and investigation of mechanisms of treatment resistance in particular related to dysfunctional cell death signaling and more recently exploring the effect on the tumour immune response.
A cohort of tumour specimens with corresponding clinical response and outcome data from patients with advanced colorectal cancer who received oxaliplatin-based chemotherapy as first line treatment has been obtained including a subgroup of matched post-chemotherapy metastatic tumour specimens. Microarray profiling and mutational analysis of this cohort is underway.
This project would involve analysis of this genomic data to:
(i) Identify potential predictive biomarkers of response to oxaliplatin-based chemotherapy in advanced colorectal cancer
(ii) To identify pre-treatment and post-treatment differential marker expression and changes in relevant signaling pathways following treatment by comparing genomic profiles of the primary tumour and matched hepatic resection and correlating this with response to treatment.
(iii) To use this pre- and post-treatment analysis to identify mechanisms associated with resistance to treatment and potential therapeutic targets to exploit to overcome drug resistance with particular interest in novel therapies that inhibit tumour cell proliferation and initiate cell death.
This project would be carried out in collaboration with Professor Dan Longley of the Drug Resistance Group.