Identifying drivers of treatment resistance in metastatic colorectal cancer

This project aims to identify which metastatic tumour cells drive treatment resistance and/or post-treatment regrowth and to characterise the mechanisms that underlie this ability.

Colorectal cancer (CRC) is one of the most common and lethal tumour types worldwide. A patient with metastatic CRC only has a 12% chance of surviving for 5 years, and each year metastatic progression leads to a fatal outcome for over 700,000 patients globally. The ultimate cause of patient fatality is metastases forming in vital organs, such as the liver.

Current therapies are often unsuccessful against metastatic tumours, which frequently recur after treatment cessation. The ability to prevent post-treatment recurrence would therefore dramatically improve patient survival. A key roadblock to achieve this goal resides in our poor understanding of intra-metastatic heterogeneity and of the different pathways that metastatic cells can use to resist treatment.

Professor Fred Hollande and team have developed biological and technological tools to enable this work, with access to freshly-resected liver metastasis samples and the use of ex-vivo (tumour organoids) and in vivo (orthotopic xenograft) preclinical models.

Their cutting-edge optical barcoding technique enables tracking of multiple tumour cell subclones over time and the purification of cell subsets that display differential behaviours in response to treatment, allowing for the analysis of both non-genetic and genetically-driven resistance mechanisms.