Characterizing metastatic heterogeneity in colorectal cancer

Project Details

A large number of cancer patients develop metastases and their survival rates are unfortunately very poor, because metastatic tumours respond poorly or start growing back after treatment has stopped. Establishment of resistance and recurrence of initially treatment-responsive tumours are likely to involve the resistance of genetically unique clones, plasticity of tumour cells and self-renewal mechanisms driven by cancer stem cell populations. Our current knowledge is insufficient to understand whether these mechanisms co-exist or whether individual tumours preferentially use one of these pathways to survive and evade treatment.

Using a combination of fluorescent and genetic barcoding techniques in vivo and in vitro, this project aims to analyse the development of tumour heterogeneity during the metastatic progression of colorectal cancer, to determine whether the heterogeneity of liver metastases impacts on their ability to interact with the immune system and to analyse how it is affected by treatment with anti-cancer compounds. Outcomes from this project will significantly improve our understanding of metastatic heterogeneity and will inform clinical treatment decisions by understanding the mechanisms that underlie post-treatment relapse.