MSC-Delivered Soluble TRAIL and Paclitaxel as Novel Combinatory Treatment for Pancreatic Adenocarcinoma

Theranostics
Filippo RossignoliMassimo Dominici

Abstract

Pancreatic cancer is the fourth leading cause of cancer death in western countries with more than 100,000 new cases per year in Europe and a mortality rate higher than 90%. In this scenario, advanced therapies based on gene therapies are emerging, thanks to a better understanding of tumour architecture and cancer cell alterations. We have demonstrated the efficacy of an innovative approach for pancreatic cancer based on mesenchymal stromal cells (MSC) genetically engineered to produce TNF-related Apoptosis Inducing Ligand (TRAIL). Here we investigated the combination of this MSC-based approach with the administration of a paclitaxel (PTX)-based chemotherapy to improve the potential of the treatment, also accounting for a possible resistance onset. Methods: Starting from the BXPC3 cell line, we generated and profiled a TRAIL-resistant model of pancreatic cancer, testing the impact of the combined treatment in vitro with specific cytotoxicity and metabolic assays. We then challenged the rationale in a subcutaneous mouse model of pancreatic cancer, assessing its effect on tumour size accounting stromal and parenchymal organization. Results: PTX was able to restore pancreatic cancer sensitivity to MSC-delivered TRAIL by reverting i...Continue Reading

Citations

Aug 25, 2019·Acta Pharmacologica Sinica·Hui-Hai ZhongYong-Zhuo Huang
Oct 30, 2020·Frontiers in Pharmacology·Giulia GolinelliGiulia Grisendi
Feb 13, 2021·Biomedical Materials·Themis R KyriakidesWendy C Sheu
Jul 30, 2021·Frontiers in Cell and Developmental Biology·Ali HassanzadehMostafa Jarahian

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Methods Mentioned

BETA
FACS
flow cytometry

Software Mentioned

GraphPad
FACS Diva
StepOne
Excel
Prism

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis