Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is associated with poor prognosis. Despite years of research and improvements in chemotherapy regimens, the 5-year survival rate of PDAC remains dismal. Therapies for PDAC often face resistance owing in large part to an extensive desmoplastic stromal matrix. Modelling PDAC ex vivo to investigate novel therapeutics is challenging due to the complex tumour microenvironment and its heterogeneity in native tumours. Development of novel therapies is needed to improve PDAC survival rates, for which disease models that recapitulate the tumour biology are expected to bear utility. This review focuses on the existing preclinical models for human PDAC and discusses advancements in tissue remodelling to guide translational PDAC research. Further emphasis is placed on photodynamic therapy (PDT) due to the ability of this treatment modality to not only directly kill cancer cells by minimally invasive means, but also to perturb the tumour microenvironment and elicit a post-therapeutic anti-tumour immune response. Accordingly, more complex preclinical models that feature multiple biologically relevant PDAC components are needed to develop translatable PDT regimens in a preclinical setting.