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Full NameProfessor Dan Longley
Department:Patrick Johnston Centre for Cancer Research
Organisation:Queen's University Belfast
- Clinical Trials
My research is focussed on the extrinsic apoptotic pathway regulated by death receptors. In particular, my work investigates the predictive, prognostic and therapeutic relevance of the caspase 8 inhibitor FLIP and the inhibitor of apoptosis proteins (IAPs). We have shown that FLIP and IAPs are key regulators of death receptor-, chemotherapy- and radiation-induced apoptosis in a range of in vitro and in vivo cancer models. Based on this work (accepted for publication in Mol Cancer Therapeutics), we are currently planning a phase-I clinical trial to examine the combination of a novel IAP inhibitor tolinapant (Astex Pharmaceuticals) with standard-of-care chemotherapy (FOLFOX) in metastatic colorectal cancer.
The projects will involve exploring novel methods to overcome resistance to standard-of-care chemotherapy in colorectal cancer. Novel mechanisms of resistance relating to cell death and immunity identified from analysis of clinical cohorts will be explored in advanced pre-clinical models of colorectal cancer. There will be a focus on direct (eg. FLIP and IAP inhibitors) and indirect (eg. histone deacetylase inhibitors) modulators of cell death and immunity, which have direct line of sight to clinical trials in biomarker-definable subgroups of patients with drug resistant, poor prognostic disease. The aim is to provide evidence for clinical trials not only in the advanced metastatic disease setting, but also in the neo-adjuvant disease setting.