Abstract
Simple SummaryPancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. Numerous clinical trials evaluating various combinations of chemotherapy and targeted agents and radiotherapy have failed to provide meaningful improvements in survival. A growing number of studies however have indicated that photodynamic therapy (PDT) may be a viable approach for treatment of some pancreatic tumors. PDT, which uses light to activate a photosensitizing agent in target tissue, has seen widespread adoption primarily for dermatological and other applications where superficial light delivery is relatively straightforward. Advances in fiber optic light delivery and dosimetry however have been leveraged to enable PDT even for challenging internal sites, including the pancreas. The aim of this article is to help inform future directions by reviewing relevant literature on the basic science, current clinical status, and potential challenges in the development of PDT as a treatment for PDAC.Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. Clinical trials of various chemotherapy, radiotherapy, targeted agents and combination strategies have generally failed to provide meaningful improvement in survival for patients with unresectable disease. Photodynamic therapy (PDT) is a photochemistry-based approach that enables selective cell killing using tumor-localizing agents activated by visible or near-infrared light. In recent years, clinical studies have demonstrated the technical feasibility of PDT for patients with locally advanced PDAC while a growing body of preclinical literature has shown that PDT can overcome drug resistance and target problematic and aggressive disease. Emerging evidence also suggests the ability of PDT to target PDAC stroma, which is known to act as both a barrier to drug delivery and a tumor-promoting signaling partner. Here, we review the literature which indicates an emergent role of PDT in clinical management of PDAC, including the potential for combination with other targeted agents and RNA medicine.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human malignancies, with a 5-year survival rate of approximately 10% in the USA [1,2]
This review focuses on the clinical and preclinical literature which explores the poThis review focuses on the clinical and preclinical literature which explores the potential role of photodynamic therapy (PDT) in clinical management of PDAC
As interstitial fluid pressure (IFP) increases to the value of microvascular pressure (MVP), the transportation of molecules to the tumor stops, which can lead to impermeability of large parts of PDAC tumor to therapeutic deliveries [41]
Summary
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human malignancies, with a 5-year survival rate of approximately 10% in the USA [1,2]. All clinical trials of chemotherapy drugs, targeted agents and combinations have failed to provide meaningful improvements in survival and most patients end up receiving palliative treatment [6,7]. Survival benefit was observed to be further lectively, these results point to the fact that there remains an urgent need for strategies to enhanced using modified FOLFIRINOX combination [10] We will examine examine how the biology of pancreatic cancer, which is characterized by prominent stromal involvement, presents challenges for drug delivery, and implications and opportunities for PDT. Cancers 2021, 13, 4354 how the biology of pancreatic cancer, which is characterized by prominent stromal involvement, presents challenges for drug delivery, and implications and opportunities for PDT
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