ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Inhibition of Hedgehog Signaling Alters Fibroblast Composition in Pancreatic Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
207 citing papers in PubMed, 1 synthesis or guideline pooled it, 268 citations in OpenAlex.
- Metabolic regulation and immunosuppressive functions of lipid-associated macrophages in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Pooled it
- Immune-featured stromal niches associate with response to neoadjuvant immunotherapy in oral squamous cell carcinoma.Cell reports. Medicine · 2025Trial
- Trial
- Biomimetic co-delivery nanoplatform overcomes CAF- and TAM-induced immunosuppression to augment therapeutic efficacy against triple-negative breast cancer.International journal of pharmaceutics: X · 2026Article
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Review
- Breaking barriers: nano-boosted drug delivery systems in overcoming the defenses of pancreatic cancer.Molecular cancer · 2026Review
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- CODAvision: best practices and a user-friendly interface for rapid, customizable segmentation of medical images.Nature protocols · 2026Review
- KIF7 promotes the proliferation of clear cell renal cell carcinoma by activating the WNT/β-catenin signaling pathway.Clinical and experimental medicine · 2026Article
- Integrative single-cell and spatial transcriptomic analysis reveals that ATG13 enriched in cancer-associated fibroblasts is associated with the suppression of ferroptosis in colorectal cancer.Discover oncology · 2026Article
- Article
- Heterogeneity of Cancer-Associated Fibroblasts and Precision Targeting Strategies for Cancer Therapy.Thoracic cancer · 2026Review
- Quantitative 3D histology reveals localized immune remodeling during early pancreatic cancer progression.Cell press blue · 2026Article
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mevalonate pathway in pancreatic ductal adenocarcinoma: Mechanisms driving metabolic and cellular plasticity.Cancer pathogenesis and therapy · 2026Review
- DeCAF defines clinical fibroblast subtypes and multidimensional tumor-stroma crosstalk shaping prognosis and immunotherapy response.Cell reports. Medicine · 2026Article
- Estrogen Production in Pancreatic Cancer Shapes a Tumor-Suppressive Stromal Microenvironment.Cancer research · 2026Article
- Article
- Modeling CAF-tumor interactions to overcome therapy resistance.Journal of experimental & clinical cancer research : CR · 2026Review
147 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors at 2 institutions in 2 countries.
Funding
Abstract
purposePancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by an extensive fibroinflammatory stroma, which includes abundant cancer-associated fibroblast (CAF) populations. PDAC CAFs are heterogeneous, but the nature of this heterogeneity is incompletely understood. The Hedgehog pathway functions in PDAC in a paracrine manner, with ligands secreted by cancer cells signaling to stromal cells in the microenvironment. Previous reports investigating the role of Hedgehog signaling in PDAC have been contradictory, with Hedgehog signaling alternately proposed to promote or restrict tumor growth. In light of the newly discovered CAF heterogeneity, we investigated how Hedgehog pathway inhibition reprograms the PDAC microenvironment. EXPERIMENTAL
designWe used a combination of pharmacologic inhibition, gain- and loss-of-function genetic experiments, cytometry by time-of-flight, and single-cell RNA sequencing to study the roles of Hedgehog signaling in PDAC.
resultsWe found that Hedgehog signaling is uniquely activated in fibroblasts and differentially elevated in myofibroblastic CAFs (myCAF) compared with inflammatory CAFs (iCAF). Sonic Hedgehog overexpression promotes tumor growth, while Hedgehog pathway inhibition with the smoothened antagonist, LDE225, impairs tumor growth. Furthermore, Hedgehog pathway inhibition reduces myCAF numbers and increases iCAF numbers, which correlates with a decrease in cytotoxic T cells and an expansion in regulatory T cells, consistent with increased immunosuppression.
conclusionsHedgehog pathway inhibition alters fibroblast composition and immune infiltration in the pancreatic cancer microenvironment.
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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.