ArticleMolecular cancer2019
Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer.
Article in Molecular cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.
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Who cites it
159 citing papers in PubMed, 1 synthesis or guideline pooled it, 289 citations in OpenAlex.
- Association of interleukin-6 gene polymorphisms with the risk of hepatocellular carcinoma: An up-to-date meta-analysis.Medicine · 2020Pooled it
- Fatty acid β-oxidation-associated prognostic model in gastric cancer and functional validation of IL-6 as a potential therapeutic target.Scientific reports · 2026Article
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Roles of interleukins in spasmolytic polypeptide‑expressing metaplasia (Review).International journal of oncology · 2026Review
- Decorin facilitates T cell-mediated antitumor immunity and augments the efficacy of anti-PD1 immunotherapy.Cancer immunology, immunotherapy : CII · 2026Article
- Hydrogen Sulfide InhibitsCells · 2026Article
- Cancer-associated fibroblast-derived GAS6 increases resistance to chemotherapy through AXL/STAT3/ABCG1 in gastric cancer.British journal of cancer · 2026Article
- Development of an early diagnostic model for gastric cancer combining serum cytokine profiles with conventional tumor markers: a case-control study.Frontiers in oncology · 2026Article
- Spatial Fibroblast-Macrophage Niches in Gastric Cancer: Mechanisms of Immune Exclusion, Therapeutic Resistance, and Targeted Intervention.OncoTargets and therapy · 2026Review
- RBM15 Enhances 5-Fluorouracil Drug Sensitivity and Suppresses Gastric Cancer Progression by Modulating N6-Methyladenosine Modification of ECT2-Dependent IGF2BP3.Research (Washington, D.C.) · 2026Article
- Clinical value of the novel inflammatory-nutritional marker PALR in predicting early postoperative recurrence of colorectal cancer.Discover oncology · 2025Article
- Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.Cancer research · 2025Review
- POSTN is exclusively activated in cancer-associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer.Molecular and clinical oncology · 2025Article
- Decoding the Plasticity of Cancer-Associated Fibroblasts: Mechanistic Insights and Precision Targeting Strategies in Gastric Cancer Progression and Therapeutic Resistance.Cell proliferation · 2025Article
- Neurotransmitters: an emerging target for therapeutic resistance to tumor immune checkpoint inhibitors.Molecular cancer · 2025Review
- Paracrine signaling in cancer-associated fibroblasts: central regulators of the tumor immune microenvironment.Journal of translational medicine · 2025Review
- Serum pro-inflammatory cytokines as potential biomarkers for the diagnosis of gastric carcinoma.World journal of clinical oncology · 2025Article
- A Novel Neutrophil Extracellular Trap Signature Predicts Patient Chemotherapy Resistance and Prognosis in Lung Adenocarcinoma.Molecular biotechnology · 2025Article
- Cancer-associated fibroblast-derived fibulin-5 promotes epithelial-mesenchymal transition in diffuse-type gastric cancer via cAMP response element-binding protein pathway, showing poor prognosis.Experimental & molecular medicine · 2025Article
- Potential predictive value of CD8A and PGF protein expression in gastric cancer patients treated with neoadjuvant immunotherapy.BMC cancer · 2025Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough the tumor stroma in solid tumors like gastric cancer (GC) plays a crucial role in chemo-resistance, specific targets to inhibit the interaction between the stromal and cancer cells have not yet been utilized in clinical practice. The present study aims to determine whether cancer-associated fibroblasts (CAFs), a major component of the tumor stroma, confer chemotherapeutic resistance to GC cells, and to discover potential targets to improve chemo-response in GC.
methodsTo identify CAF-specific proteins and signal transduction pathways affecting chemo-resistance in GC cells, secretome and transcriptome analyses were performed. We evaluated the inhibiting effect of CAF-specific protein in in vivo and in vitro models and investigated the expression of CAF-specific protein in human GC tissues.
resultsSecretome and transcriptome data revealed that interleukin-6 (IL-6) is a CAF-specific secretory protein that protects GC cells via paracrine signaling. Furthermore, CAF-induced activation of the Janus kinase 1-signal transducer and activator of transcription 3 signal transduction pathway confers chemo-resistance in GC cells. CAF-mediated inhibition of chemotherapy-induced apoptosis was abrogated by the anti-IL-6 receptor monoclonal antibody tocilizumab in various experimental models. Clinical data revealed that IL-6 was prominently expressed in the stromal portion of GC tissues, and IL-6 upregulation in GC tissues was correlated with poor responsiveness to chemotherapy.
conclusionsOur data provide plausible evidence for crosstalk between GC cells and CAFs, wherein IL-6 is a key contributor to chemoresistance. These findings suggest the potential therapeutic application of IL-6 inhibitors to enhance the responsiveness to chemotherapy in GC.
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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.