Mapping Common and Divergent Therapy-induced Remodelling of Extracellular Matrix Towards Novel Therapeutic Combinations in Pancreatic Cancer
Supervisors:
Dr Xiao Fu, School of Cancer Sciences
Prof Jen Morton, School of Cancer Sciences
Summary:
Pancreatic cancer is a devastating disease, and new therapeutic approaches are urgently needed. Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage, where the tumour is surrounded by a myriad of other cells, such as cancer-associated fibroblasts (CAFs), immune cells, and non-cellular components including the extracellular matrix (ECM). The intricate and dynamic crosstalk between the tumour and its surroundings fuels disease progression and underpins resistance to treatments.
The roles of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) in PDAC progression and responsiveness to therapy are increasingly appreciated. Nevertheless, treatment strategies targeting pancreatic stroma have been largely disappointing in the clinical setting. Given the difficulty of mapping and modelling dynamics of tumour and the TME through therapy in patients, innovative pre-clinical model systems are essential to increase insights into fundamental mechanisms of resistance and identify novel therapeutic strategies to improve treatment outcomes.
This project aims to investigate the dynamics and archetypes of ECM remodelling induced by a broad spectrum of therapies and to identify novel therapeutic combinations for better treatment outcomes. The student will work with a multidisciplinary supervisory team, integrating quantitative bioimage analysis, data science and AI (Fu lab) with pre-clinical mouse models of pancreatic cancer (Morton lab).