ArticleCancer research2018
Tumor-Stroma IL1β-IRAK4 Feedforward Circuitry Drives Tumor Fibrosis, Chemoresistance, and Poor Prognosis in Pancreatic Cancer.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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The trial behind it
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Who cites it
132 citing papers in PubMed, 188 citations in OpenAlex.
- Blockade of Tumor TAK1 Induces DNA Damage and Immunogenic cGAS-STING Pathway Activation in Pancreatic Cancer.Gastroenterology · 2026Article
- IL-37 drives temozolomide resistance in glioblastoma via MAPK pathway activation.Oncology letters · 2026Article
- Review
- An integrative machine learning and structure-driven drug repositioning strategy for human IRAK4-targeted cancer therapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Bidirectional crosstalk between cancer-associated fibroblasts and tumor immunity: shaping the microenvironment and response to immune checkpoint therapy.Experimental hematology & oncology · 2026Review
- GLIS3 marks a neural-like progenitor cell state that drives metastasis in pancreatic ductal adenocarcinoma.Cell reports · 2026Article
- An Insulin-Exosome-TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrating network pharmacology, molecular docking, and experimental validation to investigate the therapeutic effects and potential mechanisms of lycopene against pancreatic ductal adenocarcinoma.Frontiers in nutrition · 2026Article
- Metabolic Reprogramming in the Bladder Cancer Microenvironment: Bridging Fundamental Research and Therapeutic Avenues for Cancer-Associated Fibroblasts.Advances in experimental medicine and biology · 2026Review
- Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment.Cancer biology & medicine · 2025Review
- Cellular characteristics of the immune microenvironment of colorectal cancer and progress in immunotherapy research.Annals of medicine · 2025Review
- A 3D Bioprinted Pancreatic Cancer Model Using Collagen-Gelatin Methacrylamide-Alginate Bioinks to Mimic the Desmoplastic Microenvironment.Biomacromolecules · 2025Article
- IRAK signaling in cancers: mechanisms, targeting, and clinical implications.Expert opinion on investigational drugs · 2025Review
- Radioresistance Mechanisms in Head and Neck Cancer.Clinical and experimental otorhinolaryngology · 2025Review
- Safety, tolerability, and preliminary efficacy of nadunolimab, an anti-IL- 1 receptor accessory protein monoclonal antibody, in combination with pembrolizumab in patients with solid tumors.Investigational new drugs · 2025Article
- Apelin/APJ: Another Player in the Cancer Biology Network.International journal of molecular sciences · 2025Review
- Subtype-associated complexity and prognostic significance of the NLRP3 inflammasome landscape in pancreatic neoplasms.The journal of pathology. Clinical research · 2025Article
- Distinct response to IL-1β blockade in liver- and lung-specific metastasis mouse models of pancreatic cancer with heterogeneous tumor microenvironments.Experimental hematology & oncology · 2025Article
- BAP1 Represses Sequential Activation of IRAKs and NF-κB Signaling in Pancreatic Cancer.International journal of biological sciences · 2025Article
- The role of inflammatory factors in the tumor microenvironment of pancreatic cancer.Frontiers in immunology · 2025Review
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Targeting the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) holds promise to augment the effect of chemotherapy, but success in the clinic has thus far been limited. Preclinical mouse models suggest that near-depletion of cancer-associated fibroblasts (CAF) carries a risk of accelerating PDAC progression, underscoring the need to concurrently target key signaling mechanisms that drive the malignant attributes of both CAF and PDAC cells. We previously reported that inhibition of IL1 receptor-associated kinase 4 (IRAK4) suppresses NFκB activity and promotes response to chemotherapy in PDAC cells. In this study, we report that CAF in PDAC tumors robustly express activated IRAK4 and NFκB. IRAK4 expression in CAF promoted NFκB activity, drove tumor fibrosis, and supported PDAC cell proliferation, survival, and chemoresistance. Cytokine array analysis of CAF and microarray analysis of PDAC cells identified IL1β as a key cytokine that activated IRAK4 in CAF. Targeting IRAK4 or IL1β rendered PDAC tumors less fibrotic and more sensitive to gemcitabine. In clinical specimens of human PDAC, high stromal IL1β expression associated strongly with poor overall survival. Together, our studies establish a tumor-stroma IL1β-IRAK4 feedforward signal that can be therapeutically disrupted to increase chemotherapeutic efficacy in PDAC.
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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.