Translational Cancer Therapeutics

Cytotoxic drug resistance is a major cause of treatment failure in human cancer that may be driven by specific patterns of genomic instability.

We are using functional and integrative genomic approaches to identify drug specific and multi-drug resistance pathways that may enable improved targeting of common chemotherapy and targeted agents to sensitive patient cohorts. Our RNA interference screening approaches have identified several kinases that promote taxane resistance and polyploidy independent of drug treatment, indicating that pathways that regulate chromosomal stability may be functionally required for taxane response. We are currently investigating the role of regulators of chromosomal stability in the acquisition of resistance to taxanes in breast cancer and identifying mechanisms of cytotoxic chemotherapy mediated cell death using microarray expression profiling techniques combined with functional genomic validation.

Using synthetic lethal approaches in isogenic models of genomic instability we hope to identify novel survival pathways in order to limit the acquisition of drug resistance and provide new cancer-specific targets for drug discovery programmes.