ArticleCell2014
Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy.
2 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 685 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
685citing papers in PubMed, 2 pooled it
68.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
NCT02779465 phase4not yet recruitingnot on this mapstarted 2016, after this paper: background citation
Study of Oral Vitamin D Treatment for the Prevention of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B
The Effect of Vitamin D Substitution on Pancreatic Parenchyma and Development of Fibrosis After First Acute Alcoholic Pancreatitis: A Randomized Prospective Trial
Who cites it
685 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,103 citations in OpenAlex.
- Vitamin D and Pancreatic Ductal Adenocarcinoma-A Review of a Complicated Relationship.Nutrients · 2024Pooled it
- The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of observational studies.European journal of nutrition · 2024Pooled it
- Co-Clinical Evaluation of Synthetic Vitamin D and Chemotherapy in Pancreatic Cancer by Integrated Imaging and Molecular Analyses.Cancer research communications · 2026Trial
- High-Dose Vitamin D and Early Chronic Pancreatitis-Related Changes After Acute Pancreatitis: A Randomized Dose Controlled Trial.Digestive diseases and sciences · 2026Trial
- A phase II clinical trial of albumin-bound paclitaxel, cisplatin, gemcitabine (NABPLAGEM), and paricalcitol as neoadjuvant therapy in pancreatic cancer.The oncologist · 2026Trial
- Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: a randomized, multiarm, run-in phase trial.Nature cancer · 2026Trial
- Trial
- Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine.Cell reports. Medicine · 2025Trial
- Pembrolizumab ± paricalcitol in metastatic pancreatic cancer postmaximal cytoreduction.The oncologist · 2025Trial
- Multi-stromal organoid co-culture modelling reveals epithelial-fibroblast heterogeneity in pancreatic cancer and pancreatitis.Nature cell biology · 2026Article
- Zileuton protects pancreatic stellate cells from oxidative stress and ferroptosis by modulating the Nrf2 pathway and mitochondrial activity.Journal of physiology and biochemistry · 2026Article
- Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Desmoplasia and therapeutic resistance in pancreatic ductal adenocarcinoma.Cancer letters · 2026Review
- Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer.Cancer immunology research · 2026Article
- Cancer-associated fibroblasts: The silent conductors of tumor evolution and therapy refractoriness.Molecular biology reports · 2026Review
- Targeted extracellular vesicle-photoimmunotherapy remodels stromal-immune microenvironment to boost chemo-immunotherapy in preclinical models.Cell reports. Medicine · 2026Article
- VDR Activation Suppresses Pancreatic Cancer Metastasis Through Inhibition of the ERK Signaling Pathway.Cancers · 2026Article
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- Impact of vitamin D on the colon cancer immune microenvironment: results of a randomized clinical trial of preoperative vitamin D supplementation in patients with stage I-III colon cancer.Cancer discovery · 2026Article
- Intra-Tumor Heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC)-Microenvironmental Interaction and Precision Immunotherapy Strategies: A Multi-Omics-Based Integrated Perspective.International journal of molecular sciences · 2026Review
625 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 13 institutions in 4 countries.
Mara H ShermanGene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.
Ruth T YuGene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.
Dannielle D EngleCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Ning DingGene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.
Annette R AtkinsGene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.
Herve TiriacCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Eric A CollissonDepartment of Medicine/Hematology and Oncology, University of California San Francisco, San Francisco, CA 94143, USA.
Frances ConnorCancer Research UK Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge CB2 ORE, UK.
Terry Van DykeCenter for Advanced Preclinical Research, NCI-Frederick, Frederick, MD 21702, USA.
Serguei KozlovCenter for Advanced Preclinical Research, Leidos Biomed, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Philip MartinCenter for Advanced Preclinical Research, Leidos Biomed, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Tiffany W TsengGene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.
David W DawsonJonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Timothy R DonahueJonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Atsushi MasamuneDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai Miyagi, 980-8574, Japan.
Tooru ShimosegawaDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai Miyagi, 980-8574, Japan.
Minoti V AptePancreatic Research Group, Faculty of Medicine, South Western Sydney Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
Jeremy S WilsonPancreatic Research Group, Faculty of Medicine, South Western Sydney Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
Beverly NgDiabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
Sue Lynn LauDiabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2052, Australia; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia.
Jenny E GuntonDiabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2052, Australia; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia.
Geoffrey M WahlGene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.
Tony HunterMolecular and Cell Biology Laboratory, Salk Institute, La Jolla, CA 92037, USA.
Jeffrey A DrebinDepartment of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Peter J O'DwyerAbramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Christopher LiddleThe Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.
David A TuvesonCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Michael DownesGene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA. Electronic address: downes@salk.edu.
Ronald M EvansGene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA. Electronic address: evans@salk.edu.
Salk Institute for Biological Studies · USCold Spring Harbor Laboratory · USUNSW Sydney · AUThe University of Sydney · AUTohoku University · JPUniversity of California, Los Angeles · USCancer Research UK · GBFrederick National Laboratory for Cancer Research · USGarvan Institute of Medical Research · AUHospital of the University of Pennsylvania · USLeidos (United States) · USUniversity of California, San Francisco · USUniversity of Pennsylvania · US
Funding
Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9MViral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8MYeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8MHORMONAL REGULATION OF MAMMALIAN GENE EXPRESSIONR37DK057978 · NIDDK · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI EVANS, RONALD M · 2000 to 2019
$16.0MSalk Institute Cancer Training GrantT32CA009370 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Diana Clare Hargreaves, Jan Karlseder · 1986 to 2026
$8.6MTargeting diet-induced promotion of Kras-initiated pancreatic adenocarcinomaP01CA163200 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PANDOL, STEPHEN J. · 2012 to 2016
$6.2MSpatial Regulation of Developmental Gene ExpressionR01HL105278 · NHLBI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI EVANS, RONALD M · 2011 to 2019
$4.0MCSHL Cancer Gene Discovery and Cancer Biology Postdoctoral Research Training ProgramT32CA148056 · NCI · COLD SPRING HARBOR LABORATORY · PI TROTMAN, LLOYD C · 2011 to 2020
$1.8MMolecular Mechanisms of Inflammation, Steatosis and Hepatic Insulin ResistanceR24DK090962 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OLEFSKY, JERROLD MICHAEL · 2010 to 2011
$1.5MHoward Hughes Medical InstituteNCI NIH HHS CA014195NCI NIH HHS P01 CA163200NCI NIH HHS P30 CA014195NCI NIH HHS P30 CA045508NCI NIH HHS T32 CA009370NCI NIH HHS T32-CA009370NCI NIH HHS T32 CA148056NHLBI NIH HHS HL105278NHLBI NIH HHS R01 HL105278NIDDK NIH HHS DK0577978NIDDK NIH HHS DK090962NIDDK NIH HHS R24 DK090962NIDDK NIH HHS R37 DK057978NIEHS NIH HHS ES010337NIEHS NIH HHS P42 ES010337
Abstract
The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK:
Indexed as
AdenocarcinomaAnimalsAntineoplastic AgentsCalcitriolCarcinoma, Pancreatic DuctalCell Line, TumorDisease Models, AnimalGene Expression ProfilingHumansMice, Inbred C57BLMolecular Sequence DataPancreatic NeoplasmsPancreatitisReceptors, CalcitriolSignal TransductionStromal CellsAntineoplastic AgentscalcipotrieneCalcitriolReceptors, Calcitriol
Identifiers
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Registered trials
NCT02779465ClinicalTrials.gov
NCT02965898ClinicalTrials.gov
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.