Dissecting the molecular origins of biliary tract cancer

Why patients with chronic tissue inflammation and fibrosis often develop ductular cancers in their liver, gallbladder and pancreas is not understood. While screening has improved early detection and subsequent survival for some patients with cancer, those with chronic disease often present with established malignancies for which treatment options are limited. In the liver and pancreas, chronic tissue damage results in inflammation, repair and tissue scarring, where a collagen-rich matrix makes tissues stiffer. Stiffness is associated with cancer cell proliferation in established tumours; though how chronic inflammation and scarring makes tissues more susceptible to tumour initiation remains unclear. Across organs, genetic mutations are often insufficient to drive cancer formation. As such, the Liver Growth and Cancer lab are interested in identifying additional tumour-initiating factors that enable mutant cells to form neoplasms. Specifically, we address how, during organ repair, changing fibroinflammatory landscapes regulate ductular disease and ask how cancer cells hijack this regenerative response to promote tumour initiation. Leveraging this information, we dissect how ductular pre-cursor lesions begin in high-risk patients. Understanding the origins of cancer in chronic disease will enable us to detect cancer earlier and by specifically uncoupling tumour-initiating cells from their microenvironment, we propose we can prevent cancer progression in those high-risk patients with chronic inflammatory disease.