John W Cassidy
Large-scale genomics projects such as The Cancer Genome Atlas and METABRIC have begun to unravel the diverse heterogeneity of human malignancies. Further to this intertumour heterogeneity, recent studies have highlighted the heterogeneity within a single tumour (intratumour heterogeneity). Although it is beginning to become apparent that clonal populations within a tumour can have clinically relevant effects, we are far from understanding the drivers of clonal dynamics.
Patient-derived tumour xenografts (PDXs) have emerged as a powerful technology capable of retaining the molecular heterogeneity of their originating sample. Our research aims to fully describe the clonal dynamics in a panel of breast cancer PDX models, how these vary between models and how clonal dynamics are affected by passage. Furthermore, we will investigate the clonal dynamics involved in the development of drug resistance and strategies to perturb these dynamics with novel therapeutics.