ArticleOncotarget2016
A module of inflammatory cytokines defines resistance of colorectal cancer to EGFR inhibitors.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The autocrine loop of ALK receptor and ALKAL2 ligand is an actionable target in consensus molecular subtype 1 colon cancer.Journal of experimental & clinical cancer research : CR · 2022Pooled it
- PLCG1 regulates pyroptosis to inhibit the progression of non-small cell lung cancer: A Mendelian randomization study.Medicine · 2026Article
- Article
- Nutrients Lowering Obesity-Linked Chemokines Blamable for Metastasis.International journal of molecular sciences · 2025Review
- An overview of mechanisms, biomarkers, and treatment strategies for acquired anti-EGFR resistance in RAS wild-type colorectal cancer.Frontiers in pharmacology · 2025Review
- A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms.Annals of surgical oncology · 2023Article
- New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance.ACS central science · 2023Article
- An Overview of the Potential Medicinal and Pharmaceutical Properties of Ru(II)/(III) Complexes.International journal of molecular sciences · 2023Review
- Senescence-associated reprogramming induced by interleukin-1 impairs response to EGFR neutralization.Cellular & molecular biology letters · 2022Article
- IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy.Frontiers in cell and developmental biology · 2022Review
- Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer.Cancers · 2021Article
- Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions.Journal of neuroinflammation · 2021Article
- Morphological study of TNPO3 and SRSF1 interaction during myogenesis by combining confocal, structured illumination and electron microscopy analysis.Molecular and cellular biochemistry · 2021Article
- Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury.International journal of molecular sciences · 2021Review
- Skin inflammatory response and efficacy of anti-epidermal growth factor receptor therapy in metastatic colorectal cancer (CUTACETUX).Oncoimmunology · 2020Article
- Overcoming malignant cell-based mechanisms of resistance to immune checkpoint blockade antibodies.Seminars in cancer biology · 2020Review
- Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies.International journal of molecular sciences · 2020Review
- CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers.Frontiers in immunology · 2020Review
- TLR4 activation leads to anti-EGFR therapy resistance in head and neck squamous cell carcinoma.American journal of cancer research · 2020Article
- Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal Growth Factor Receptor (EGFR) activates a robust signalling network to which colon cancer tumours often become addicted. Cetuximab, one of the monoclonal antibodies targeting this pathway, is employed to treat patients with colorectal cancer. However, many patients are intrinsically refractory to this treatment, and those who respond develop secondary resistance along time. Mechanisms of cancer cell resistance include either acquisition of new mutations or non genomic activation of alternative signalling routes. In this study, we employed a colon cancer model to assess potential mechanisms driving resistance to cetuximab. Resistant cells displayed increased ability to grow in suspension as colonspheres and this phenotype was associated with poorly organized structures. Factors secreted from resistant cells were causally involved in sustaining resistance, indeed administration to parental cells of conditioned medium collected from resistant cells was sufficient to reduce cetuximab efficacy. Among secreted factors, we report herein that a signature of inflammatory cytokines, including IL1A, IL1B and IL8, which are produced following EGFR pathway activation, was associated with the acquisition of an unresponsive phenotype to cetuximab in vitro. This signature correlated with lack of response to EGFR targeting also in patient-derived tumour xenografts. Collectively, these results highlight the contribution of inflammatory cytokines to reduced sensitivity to EGFR blockade and suggest that inhibition of this panel of cytokines in combination with cetuximab might yield an effective treatment strategy for CRC patients refractory to anti-EGFR targeting.
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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.