Photodynamic Stromal Depletion in Pancreatic Ductal Adenocarcinoma

Simple Summary Pancreatic cancer remains one of the deadliest cancers and has a dismal survival rate. The disease is known to be resistant to chemo- and radiotherapy, and surgery can only be curative in a small percentage of patients. It is thought that the thick tissue (stroma) surrounding the cancer cells is the main factor in the resistance to systemic therapy. Photodynamic therapy (PDT) is a new treatment that uses a specific light to activate a smart molecule to cause cancer cell death. Emerging evidence suggests that PDT may offer a solution that can alter the stroma and kill pancreatic cancer cells. The aim of this review is to summarise the literature and explore the effect of PDT on the stroma within pancreatic cancer in order to improve our understanding of this new therapy and its application.Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid malignancies, with a five-year survival of less than 10%. The resistance of the disease and the associated lack of therapeutic response is attributed primarily to its dense, fibrotic stroma, which acts as a barrier to drug perfusion and permits tumour survival and invasion. As clinical trials of chemotherapy (CT), radiotherapy (RT), and targeted agents have not been successful, improving the survival rate in unresectable PDAC remains an urgent clinical need. Photodynamic stromal depletion (PSD) is a recent approach that uses visible or near-infrared light to destroy the desmoplastic tissue. Preclinical evidence suggests this can resensitise tumour cells to subsequent therapies whilst averting the tumorigenic effects of tumour-stromal cell interactions. So far, the pre-clinical studies have suggested that PDT can successfully mediate the destruction of various stromal elements without increasing the aggressiveness of the tumour. However, the complexity of this interplay, including the combined tumour promoting and suppressing effects, poses unknowns for the clinical application of photodynamic stromal depletion in PDAC.