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Published on: November 19, 2019
Photodynamic Stromal Depletion in Pancreatic Ductal Adenocarcinoma
Nicole Lintern1, Andrew M Smith2, David G Jayne2
1School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Abstract:
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.
Insights
Photodynamic stromal depletion (PSD) shows promise for treating pancreatic cancer by targeting its dense stroma. This approach may resensitize tumors to therapies, offering hope for unresectable pancreatic ductal adenocarcinoma (PDAC).
Area of Science:
- Oncology
- Biomedical Engineering
- Photomedicine
Background:
- Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a five-year survival rate below 10%.
- Tumor resistance and poor therapeutic response in PDAC are linked to its dense, fibrotic stroma, hindering drug delivery and promoting tumor growth and invasion.
- Current treatments including chemotherapy, radiotherapy, and targeted agents have limited success in unresectable PDAC, highlighting an urgent need for novel therapeutic strategies.
Purpose of the Study:
- To explore photodynamic stromal depletion (PSD) as a novel therapeutic approach for pancreatic ductal adenocarcinoma (PDAC).
- To investigate the potential of PSD to overcome treatment resistance by targeting the tumor's desmoplastic stroma.
- To evaluate the effects of PSD on tumor cells and stromal interactions in preclinical models of PDAC.
Main Methods:
- Utilizing photodynamic therapy (PDT) principles with visible or near-infrared light to target and ablate the desmoplastic stroma in PDAC models.
- Assessing the impact of PSD on stromal components and their barrier function.
- Evaluating the potential of PSD to resensitize PDAC cells to subsequent therapies.
- Analyzing the complex tumor-stromal interactions, including both tumor-promoting and tumor-suppressing effects.
Main Results:
- Preclinical studies indicate that PSD can effectively destroy various stromal elements within the tumor microenvironment.
- Evidence suggests PSD can resensitize tumor cells to subsequent therapeutic interventions.
- PSD has shown potential in averting the pro-tumorigenic effects associated with tumor-stromal cell interactions.
- Initial findings suggest PSD does not increase tumor aggressiveness.
Conclusions:
- Photodynamic stromal depletion (PSD) presents a promising strategy for managing pancreatic ductal adenocarcinoma (PDAC) by targeting its fibrotic stroma.
- PSD may enhance the efficacy of conventional therapies by improving drug perfusion and overcoming treatment resistance.
- Further research is needed to fully understand the complex tumor-stromal interplay and optimize PSD for clinical application in PDAC.
