ArticleEMBO molecular medicine2015
Pharmacological targeting of the protein synthesis mTOR/4E-BP1 pathway in cancer-associated fibroblasts abrogates pancreatic tumour chemoresistance.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.
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Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.
- Collagenase-mediated extracellular matrix targeting for enhanced drug penetration and therapeutic efficacy in nanoscale delivery systems for cancer therapy.Journal of nanobiotechnology · 2025Pooled it
- Breast cancer-associated fibroblast-derived exosomal miR-1290 promotes triple-negative breast cancer cell proliferation.Signal transduction and targeted therapy · 2026Article
- Immune-driven stromal inflammation in pancreatic cancer within a microfluidic platform.Biofabrication · 2026Article
- PI3K and MAPK Signaling Nodes Serve as Divergent Drivers of Phenotypic Plasticity in Cancer-Associated Fibroblasts in Colorectal Cancer.Cancer research · 2026Article
- Collagen-derived biomarkers reveal distinct fibrotic responses among cancer-associated fibroblasts.Scientific reports · 2026Article
- An Insulin-Exosome-TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protocol for analyzing immune cell infiltration in 3D pancreatic heterotypic spheroids composed of tumor cells and cancer-associated fibroblasts.STAR protocols · 2026Article
- Nanomedicine for targeting cancer-associated fibroblasts in cancer therapy.Theranostics · 2026Review
- Pancreatic cancer-associated myofibroblasts: a review.International journal of biological sciences · 2026Review
- Reversible chemoresistance of pancreatic cancer grown as spheroids.Journal of chemotherapy (Florence, Italy) · 2025Article
- Establishment of U-87MG Cellular Fibrosis as a Novel in Vitro Model to Analyze Glioblastoma Cells' Sensitivity to Temozolomide.International journal of molecular sciences · 2025Article
- The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patients.BJC reports · 2025Article
- Cancer associated fibroblasts in cancer development and therapy.Journal of hematology & oncology · 2025Review
- ATR inhibition potentiates FOLFIRINOX cytotoxic effect in models of pancreatic ductal adenocarcinoma by remodelling the tumour microenvironment.British journal of cancer · 2025Article
- Chemoresistance in Pancreatic Cancer: The Role of Adipose-Derived Mesenchymal Stem Cells and Key Resistance Genes.International journal of molecular sciences · 2025Article
- Systematic analysis of anoikis-related genes identifies SRPX2-FAK/AKT-IL-6 axis in the progression and peritoneal metastasis of gastric cancer.Frontiers in genetics · 2025Article
- Bilayer 3D co-culture platform inducing the differentiation of normal fibroblasts into cancer-associated fibroblast like cells: New in vitro source to obtain cancer-associated fibroblasts.Bioengineering & translational medicine · 2025Article
- A Comprehensive Exploration of Agents Targeting Tumor Microenvironment: Challenges and Future Perspectives.Journal of immunotherapy and precision oncology · 2024Review
- The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.Cancer cell international · 2024Review
- Agonists, Antagonists and Receptors of Somatostatin: Pathophysiological and Therapeutical Implications in Neoplasias.Current issues in molecular biology · 2024Review
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is extremely stroma-rich. Cancer-associated fibroblasts (CAFs) secrete proteins that activate survival and promote chemoresistance of cancer cells. Our results demonstrate that CAF secretome-triggered chemoresistance is abolished upon inhibition of the protein synthesis mTOR/4E-BP1 regulatory pathway which we found highly activated in primary cultures of α-SMA-positive CAFs, isolated from human PDAC resections. CAFs selectively express the sst1 somatostatin receptor. The SOM230 analogue (Pasireotide) activates the sst1 receptor and inhibits the mTOR/4E-BP1 pathway and the resultant synthesis of secreted proteins including IL-6. Consequently, tumour growth and chemoresistance in nude mice xenografted with pancreatic cancer cells and CAFs, or with pieces of resected human PDACs, are reduced when chemotherapy (gemcitabine) is combined with SOM230 treatment. While gemcitabine alone has marginal effects, SOM230 is permissive to gemcitabine-induced cancer cell apoptosis and acts as an antifibrotic agent. We propose that selective inhibition of CAF protein synthesis with sst1-directed pharmacological compounds represents an anti-stromal-targeted therapy with promising chemosensitization potential.
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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.