ArticleNature communications2015
STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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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.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- CircSMEK1 Suppresses HCC via the hnRNPK-IGF2-AKT Axis: A Diagnostic Biomarker and Therapeutic Target.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CXCL8 may serve as a potential biomarker for predicting the prognosis and immune response in cervical cancer.Discover oncology · 2024Article
- The tobacco-specific carcinogen NNK induces pulmonary tumorigenesis via nAChR/Src/STAT3-mediated activation of the renin-angiotensin system and IGF-1R signaling.Experimental & molecular medicine · 2023Article
- IGF2: A Role in Metastasis and Tumor Evasion from Immune Surveillance?Biomedicines · 2023Review
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology.Frontiers in pharmacology · 2022Review
- SHP2 inhibition enhances the anticancer effect of Osimertinib in EGFR T790M mutant lung adenocarcinoma by blocking CXCL8 loop mediated stemness.Cancer cell international · 2021Article
- Lessons to Learn for Adequate Targeted Therapy Development in Metastatic Colorectal Cancer Patients.International journal of molecular sciences · 2021Review
- Development of the phenylpyrazolo[3,4-Theranostics · 2021Article
- Targeting STAT3 Abrogates Tim-3 Upregulation of Adaptive Resistance to PD-1 Blockade on Regulatory T Cells of Melanoma.Frontiers in immunology · 2021Article
- TAFs contributes the function of PTPN2 in colorectal carcinogenesis through activating JAK/STAT signaling pathway.American journal of cancer research · 2021Article
- Trop2 binding IGF2R induces gefitinib resistance in NSCLC by remodeling the tumor microenvironment.Journal of Cancer · 2021Article
- Advances of Targeted Therapy for Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Fanconi Anemia Pathway Genes Advance Cervical CancerFrontiers in cell and developmental biology · 2021Article
- Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.Journal of hematology & oncology · 2020Review
- Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion.Cell communication and signaling : CCS · 2020Article
- Microenvironmental Determinants of Breast Cancer Metastasis: Focus on the Crucial Interplay Between Estrogen and Insulin/Insulin-Like Growth Factor Signaling.Frontiers in cell and developmental biology · 2020Review
- The Role of Tyrosine Kinases as a Critical Prognostic Parameter and Its Targeted Therapies in Ewing Sarcoma.Frontiers in cell and developmental biology · 2020Review
- Article
- Therapeutic Targeting of the IGF Axis.Cells · 2019Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Drug resistance is a major impediment in medical oncology. Recent studies have emphasized the importance of the tumour microenvironment (TME) to innate resistance, to molecularly targeted therapies. In this study, we investigate the role of TME in resistance to cixutumumab, an anti-IGF-1R monoclonal antibody that has shown limited clinical efficacy. We show that treatment with cixutumumab accelerates tumour infiltration of stromal cells and metastatic tumour growth, and decreases overall survival of mice. Cixutumumab treatment stimulates STAT3-dependent transcriptional upregulation of IGF-2 in cancer cells and recruitment of macrophages and fibroblasts via paracrine IGF-2/IGF-2R activation, resulting in the stroma-derived CXCL8 production, and thus angiogenic and metastatic environment. Silencing IGF-2 or STAT3 expression in cancer cells or IGF-2R or CXCL8 expression in stromal cells significantly inhibits the cancer-stroma communication and vascular endothelial cells' angiogenic activities. These findings suggest that blocking the STAT3/IGF-2/IGF-2R intercellular signalling loop may overcome the adverse consequences of anti-IGF-1R monoclonal antibody-based therapies.
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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.