Determining the efficacy and safety of cancer chemotherapeutics for cholangiocarcinoma (CCA) using Human Precision Cut Tissue Slices (hPCTS)

Why did we fund this project?

This award aims to replace the use of mice in some studies of bile duct cancer using an ex vivo method to culture human tissue slices.

Bile duct cancer is typically studied in mice, either by implanting tumour tissue from patients or through the introduction of relevant genetic mutations. The percentage of mice that possess the mutation as a result of these programmes is small, increasing the number of animals needing to be bred to ensure enough animals for studies. The resulting tumour burden can result in pain, weight loss and other clinical signs associated with suffering. Human tissue can be cultured ex vivo and has a number of advantages over traditional in vitro methods as the precision cut tissue slices retain all relevant cell types in a 3D environment.

Dr Laura Randle will establish human precision cut tissue slices method in her laboratory receiving training, expertise and advice from her European and American collaborators on working with human tissue. Laura will confirm the validate the model for clinical relevance by analysing tissue response to chemotherapy drugs currently used in patient treatment.

• Further funding: NC3Rs PhD Studentship (£90,000), Manipulating cholangiocarcinoma immune-phenotype in a patient derived precision-cut tumour model to improve immune checkpoint inhibition response