ArticleOncogene2022
Pharmacologic conversion of cancer-associated fibroblasts from a protumor phenotype to an antitumor phenotype improves the sensitivity of pancreatic cancer to chemotherapeutics.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05064618 (Phase I/II Investigator-initiated Clinical Trial of MIKE-1 With Gemcitabine and Nab-paclitaxel Combination Therapy for Unresectable Pancreatic Cancer), which is not on this map. Cited by 48 papers.
What it found
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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.
Phase I/II Investigator-initiated Clinical Trial of MIKE-1 With Gemcitabine and Nab-paclitaxel Combination Therapy for Unresectable Pancreatic Cancer
Who cites it
48 citing papers in PubMed, 59 citations in OpenAlex.
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- Local, but not circulating, complement C3 shapes immune checkpoint blockade efficacy by controlling myeloid cell infiltration.Nature communications · 2026Article
- Meflin confers antifibrotic properties to intestinal fibroblasts in inflammatory bowel disease.The Journal of clinical investigation · 2026Article
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Increased Meflin Expression in Cancer-Associated Fibroblasts Restrains Tumor Cell Proliferation and Shapes Vessel-Rich Stroma in Triple-Negative Breast Cancer.The American journal of pathology · 2026Article
- Single cell and spatial sequencing analysis of cancer associated fibroblasts in the brain metastasis tumor microenvironment.Communications biology · 2026Article
- From CAF subtypes to clinically relevant states: cancer-associated fibroblasts in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Review
- Cancer-Associated Fibroblast-Targeted Nanomedicine in Solid Tumor Therapy: From Mechanisms of Therapeutic Resistance to Precision Stromal Modulation.International journal of nanomedicine · 2026Review
- Novel anti-tumor strategies: targeting the crosstalk between cancer stem cells and cancer-associated fibroblasts to resist drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression.Frontiers in immunology · 2026Review
- Impact of pancreatic proenzymes on pancreatic ductal adenocarcinoma associated fibroblasts.Scientific reports · 2025Article
- Meflin is a druggable target using antibody-drug conjugates in progressive osteosarcoma.Oncogene · 2025Article
- Polyethyleneimine-Assisted Fabrication of Poly(Lactic-Co-Glycolic Acid) Nanoparticles Loaded with Tamibarotene (Am80) for Meflin Expression Upregulation.Journal of functional biomaterials · 2025Article
- How Do Cancer Cells Create Cancer-Associated Fibroblast Subtypes? Impacts of Extracellular Vesicles on Stromal Diversity.Cancer science · 2025Review
- Cancer-associated fibroblasts in cancer drug resistance and cancer progression: a review.Cell death discovery · 2025Review
- p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts.Cancer science · 2025Article
- Meflin/Islr is a marker of fibroblasts that arise in fibrotic regions after spinal cord injury.Nagoya journal of medical science · 2025Article
- Stiff extracellular matrix activates the transcription factor ATF5 to promote the proliferation of cancer cells.iScience · 2025Article
- Targeting Cancer-Associated Fibroblasts: Eliminate or Reprogram?Cancer science · 2025Review
- Superoxide dismutase 2 deficiency in mesenchymal stromal cells induces sympathetic denervation and functional impairment of brown adipose tissue.Pathology international · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their proliferation in pancreatic ductal adenocarcinoma (PDAC) were not successful in mice or patients. Thus, CAFs may be tumor suppressive or heterogeneous, with distinct cancer-restraining and -promoting CAFs (rCAFs and pCAFs, respectively). Here, we showed that induced expression of the glycosylphosphatidylinositol-anchored protein Meflin, a rCAF-specific marker, in CAFs by genetic and pharmacological approaches improved the chemosensitivity of mouse PDAC. A chemical library screen identified Am80, a synthetic, nonnatural retinoid, as a reagent that effectively induced Meflin expression in CAFs. Am80 administration improved the sensitivity of PDAC to chemotherapeutics, accompanied by increases in tumor vessel area and intratumoral drug delivery. Mechanistically, Meflin was involved in the suppression of tissue stiffening by interacting with lysyl oxidase to inhibit its collagen crosslinking activity. These data suggested that modulation of CAF heterogeneity may represent a strategy for PDAC treatment.
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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.