ArticleProceedings of the National Academy of Sciences of the United States of America2014
Stromal response to Hedgehog signaling restrains pancreatic cancer progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 335 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
335 citing papers in PubMed, 1 synthesis or guideline pooled it, 492 citations in OpenAlex.
- Serum levels of iCAF-derived osteoglycin predict favorable outcome in pancreatic cancer.International journal of cancer · 2023Pooled it
- Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Midazolam Reduces Metabolic Viability and Induces Apoptosis in MIA PaCa-2 Pancreatic Cancer Cells with Selective Transcriptional Modulation of Wnt and Hedgehog Components: A Preliminary In Vitro Study.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Article
- Targeted extracellular vesicle-photoimmunotherapy remodels stromal-immune microenvironment to boost chemo-immunotherapy in preclinical models.Cell reports. Medicine · 2026Article
- Breaking barriers: nano-boosted drug delivery systems in overcoming the defenses of pancreatic cancer.Molecular cancer · 2026Review
- Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering.Journal of hematology & oncology · 2026Review
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Colony-stimulating factor-2 triggers NNMT-dependent myofibroblast activation in head and neck cancer.Oncogene · 2026Article
- A tumor microenvironment integrated (TMI) staging system for pancreatic ductal adenocarcinoma based on cancer-associated fibroblast and molecular consensus signatures.Discover oncology · 2026Article
- DeCAF defines clinical fibroblast subtypes and multidimensional tumor-stroma crosstalk shaping prognosis and immunotherapy response.Cell reports. Medicine · 2026Article
- Wilms Tumor 1-Expressing Stromal Cells Promote Pancreatic Cancer Progression.Cancer research · 2026Article
- Modeling CAF-tumor interactions to overcome therapy resistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Spatial Profiling Identified Senescent Cancer-Associated Fibroblasts Localized in the Border Region of Human Pancreatic Ductal Adenocarcinoma.Cellular and molecular gastroenterology and hepatology · 2026Article
- Mucin 5ac modulates cancer-associated fibroblast heterogeneity through epigenetic reprogramming of precursor cells.American journal of physiology. Cell physiology · 2026Article
- Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment.Cancer biology & medicine · 2025Review
- Nanotechnology-enhanced immunotherapies for pancreatic ductal adenocarcinoma: challenges and opportunities.Drug delivery and translational research · 2025Review
- Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis.bioRxiv : the preprint server for biology · 2025Article
275 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDA) is the most lethal of common human malignancies, with no truly effective therapies for advanced disease. Preclinical studies have suggested a therapeutic benefit of targeting the Hedgehog (Hh) signaling pathway, which is activated throughout the course of PDA progression by expression of Hh ligands in the neoplastic epithelium and paracrine response in the stromal fibroblasts. Clinical trials to test this possibility, however, have yielded disappointing results. To further investigate the role of Hh signaling in the formation of PDA and its precursor lesion, pancreatic intraepithelial neoplasia (PanIN), we examined the effects of genetic or pharmacologic inhibition of Hh pathway activity in three distinct genetically engineered mouse models and found that Hh pathway inhibition accelerates rather than delays progression of oncogenic Kras-driven disease. Notably, pharmacologic inhibition of Hh pathway activity affected the balance between epithelial and stromal elements, suppressing stromal desmoplasia but also causing accelerated growth of the PanIN epithelium. In striking contrast, pathway activation using a small molecule agonist caused stromal hyperplasia and reduced epithelial proliferation. These results indicate that stromal response to Hh signaling is protective against PDA and that pharmacologic activation of pathway response can slow tumorigenesis. Our results provide evidence for a restraining role of stroma in PDA progression, suggesting an explanation for the failure of Hh inhibitors in clinical trials and pointing to the possibility of a novel type of therapeutic intervention.
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What OpenQuestion holds
Registered trials
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.