ArticleCancer research2019
Deoxycytidine Release from Pancreatic Stellate Cells Promotes Gemcitabine Resistance.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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The trial behind it
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Who cites it
86 citing papers in PubMed, 166 citations in OpenAlex.
- Ribonucleotides Amplify Mitochondrial DNA-Driven cGAS-STING Activation via FdUMP-ribonucleotide Hybrid Particles to Potentiate Chemoimmunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitophagy-Competent Cancer-Associated Fibroblasts Fuel Chemoresistance by Rewiring Pyrimidine Metabolism in Pancreatic Cancer.Cancer research · 2026Article
- ATM Deficiency Induces TGFβ-Mediated Stromal Programming in Pancreatic Cancer.Cancer research · 2026Article
- Metabolic Salvage and Acyl-chain Remodeling Support Glycosphingolipid Synthesis within the PDAC Tumor Microenvironment.bioRxiv : the preprint server for biology · 2026Article
- pH-Dependent Microenvironmental Ionic Signaling in Pancreatic Ductal Adenocarcinoma.Acta physiologica (Oxford, England) · 2026Review
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Current Advances in Preclinical Patient-Derived Cultivation Models for Individualized Drug Response Prediction in Pancreatic Cancer.Oncology research · 2026Review
- Cancer-associated fibroblasts: central players in cancer hallmarks and therapeutic resistance.Cell communication and signaling : CCS · 2025Review
- Impact of pancreatic proenzymes on pancreatic ductal adenocarcinoma associated fibroblasts.Scientific reports · 2025Article
- Tumor-stromal metabolic crosstalk in pancreatic cancer.Trends in cell biology · 2025Review
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Mevalonate Biosynthesis is a Metabolic Vulnerability of Gemcitabine-resistant Pancreatic Cancer.bioRxiv : the preprint server for biology · 2025Article
- Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis.bioRxiv : the preprint server for biology · 2025Article
- Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- Phosphorylation of USP33 by CDK1 stabilizes the mTORC2 component SIN1.Cell death & disease · 2025Article
- What's on the menu?: metabolic constraints in the pancreatic tumor microenvironment.The Journal of clinical investigation · 2025Review
- Metabolomic analysis of rat arterial serum under hypobaric hypoxia: Adaptive regulation of physiological systems by metabolic reprogramming.Biochemistry and biophysics reports · 2025Article
- Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025Review
- The Role of Exosomes as a Key Factor of Cytostatic Resistance in Cancer: Mechanisms of Action, Potential Biomarkers, and Possible Exosome-Based Therapies.Oncology research · 2025Review
- Pathological complete response following neoadjuvant chemotherapy with PD-1 inhibitor for locally advanced pancreatic cancer: case report.Journal of gastrointestinal oncology · 2024Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analogue gemcitabine is among the most effective therapies to treat PDAC, however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDAC is a striking accumulation of stromal tissue surrounding the tumor, and this accumulation of stroma can contribute to therapy resistance. To better understand how stroma limits response to therapy, we investigated cell-extrinsic mechanisms of resistance to gemcitabine. Conditioned media from pancreatic stellate cells (PSC), as well as from other fibroblasts, protected PDAC cells from gemcitabine toxicity. The protective effect of PSC-conditioned media was mediated by secretion of deoxycytidine, but not other deoxynucleosides, through equilibrative nucleoside transporters. Deoxycytidine inhibited the processing of gemcitabine in PDAC cells, thus reducing the effect of gemcitabine and other nucleoside analogues on cancer cells. These results suggest that reducing deoxycytidine production in PSCs may increase the efficacy of nucleoside analog therapies. SIGNIFICANCE: This study provides important new insight into mechanisms that contribute to gemcitabine resistance in PDAC and suggests new avenues for improving gemcitabine efficacy.
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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.