ArticleBiomaterials2019
Modulation of redox metabolism negates cancer-associated fibroblasts-induced treatment resistance in a heterotypic 3D culture platform of pancreatic cancer.
Article in Biomaterials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 73 citations in OpenAlex.
- Breaking barriers: nano-boosted drug delivery systems in overcoming the defenses of pancreatic cancer.Molecular cancer · 2026Review
- Deciphering the Anti-Tumor Mechanisms of Metformin Through Reprogramming of the Tumor Microenvironment.Cells · 2026Review
- Photodynamic Therapy Combined with Anticancer Drug Therapy in the Treatment of Malignant Neoplasms.Cells · 2026Review
- The research advances of crosstalk between cancer-associated fibroblasts and tumor cells using co-culture organoids.Cell death & disease · 2026Review
- Biomolecule-Photosensitizer Conjugates: A Strategy to Enhance Selectivity and Therapeutic Efficacy in Photodynamic Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review).International journal of oncology · 2025Review
- Molecular Imaging: Unveiling Metabolic Abnormalities in Pancreatic Cancer.International journal of molecular sciences · 2025Review
- Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation.Cell death & disease · 2025Article
- Engineering Radiocatalytic Nanoliposomes with Hydrophobic Gold Nanoclusters for Radiotherapy Enhancement.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- Engineering photodynamics for treatment, priming and imaging.Nature reviews bioengineering · 2024Article
- Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian CancerPhotochemistry and photobiology · 2023Review
- Recent Advances in Cellular Signaling Interplay between Redox Metabolism and Autophagy Modulation in Cancer: An Overview of Molecular Mechanisms and Therapeutic Interventions.Antioxidants (Basel, Switzerland) · 2023Review
- Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy.Cancers · 2023Review
- Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment.Cancers · 2023Review
- Key aspects for conception and construction of co-culture models of tumor-stroma interactions.Frontiers in bioengineering and biotechnology · 2023Review
- Targeting of the tumor immune microenvironment by metformin.Journal of cell communication and signaling · 2022Review
- Remediating Desmoplasia with EGFR-Targeted Photoactivable Multi-Inhibitor Liposomes Doubles Overall Survival in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Eutectic Gallium-Indium Nanoparticles for Photodynamic Therapy of Pancreatic Cancer.ACS applied nano materials · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The complex interplay between cancer cells and their microenvironment remains a major challenge in the design and optimization of treatment strategies for pancreatic ductal adenocarcinoma (PDAC). Recent investigations have demonstrated that mechanistically distinct combination therapies hold promise for treatment of PDAC, but effective clinical translation requires more accurate models that account for the abundant tumor-stroma and its influence on cancer growth, metabolism and treatment insensitivity. In this study, a modular 3D culture model that comprised PDAC cells and patient-derived cancer-associated fibroblasts (CAFs) was developed to assess the effects of PDAC-CAF interactions on treatment efficacies. Using newly-developed high-throughput imaging and image analysis tools, it was found that CAFs imparted a notable and statistically significant resistance to oxaliplatin chemotherapy and benzoporphyrin derivative-mediated photodynamic therapy, which associated with increased levels of basal oxidative metabolism. Increased treatment resistance and redox states were similarly observed in an orthotopic xenograft model of PDAC in which cancer cells and CAFs were co-implanted in mice. Combination therapies of oxaliplatin and PDT with the mitochondrial complex I inhibitor metformin overcame CAF-induced treatment resistance. The findings underscore that heterotypic microtumor culture models recapitulate metabolic alterations stemming from tumor-stroma interactions. The presented infrastructure can be adapted with disease-specific cell types and is compatible with patient-derived tissues to enable personalized screening and optimization of new metabolism-targeted treatment regimens for pancreatic cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.