Analysis of tumour-stroma heterogeneity in human pancreatic cancer and pancreatic diseases
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Duration of Study in the UK
5 years, 0 months, 1 days
Pancreatic cancer is highly lethal, with only 1 in 10 patients surviving the first 5 years. Pancreatic tumours are complex consisting of tumour cells along with other cell types, such as fibroblasts and immune cells along with a dense, fibrous matrix collectively called stroma. This stroma can make up to 90% of the tumour, and makes tumours resistant to treatment.
Within the stroma, fibroblasts are the most abundant cell type. There are different types of fibroblasts, and their contribution to tumour growth and treatment resistance is poorly understood. There is evidence to suggest that some types of fibroblasts increase tumour growth and drug resistance, and others have the opposite effect. Therefore, we aim to understand how cancer cells and fibroblasts interact and affect each other.
To address this, we have developed model systems in the lab, including mouse pancreatic tumour organoid/fibroblast co-cultures and mouse models that largely mimic human PDAC. In combination with these models, we use drugs and genetic approaches to characterize the roles and dynamic nature of the different types of fibroblasts during different stages of pancreatic cancer progression. Although laboratory models have so far been instrumental in our understanding of pancreatic tumours, we still have limited information about the composition of the pancreatic cancer microenvironment in human PDAC. To this end, the analysis of patient samples will be essential to advance our knowledge of the roles of fibroblasts and to identify new potential targets for treatment. Altogether, our studies will determine how different fibroblast types interact with other cell types in the tumour and support pancreatic cancer progression. This analysis will help identify new treatments/combinations to selectively target the fibroblasts that promote tumour growth.
West Midlands - Black Country Research Ethics Committee
Date of REC Opinion
9 Jun 2021
Further Information Favourable Opinion