Abstract
A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its poor prognosis that stems from a marked resistance to therapy, an invasive nature, and a high metastatic potential. Photodynamic therapy (PDT) is a promising modality for effectively managing PDAC both preclinically and clinically. While clinical trials of PDT for PDAC are still in their early stages, a plethora of elegant preclinical studies are supporting the translation and clinical adoption of PDT-based treatment regimens, many of which leverage orthotopic preclinical models of PDAC. Given the aggressiveness of the disease that is largely dependent on the localization of PDAC tumors, it is imperative that preclinical models used to evaluate PDT-based treatment regimens recapitulate elements of the natural pathogenesis in order to design treatment regimens tailored to PDAC with the highest potential for clinical success. In light of the importance of clinically relevant models of PDAC, this chapter details and discusses the methodologies developed over the last three decades to leverage orthotopic PDAC models in order to evaluate PDT-based treatment regimens. The shortcomings of these are also discussed, in addition to the future directions that the field is headed to establish the most relevant orthotopic models of PDAC.