ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Establishment and characterization of a model of acquired resistance to epidermal growth factor receptor targeting agents in human cancer cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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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
55 citing papers in PubMed, 96 citations in OpenAlex.
- Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.Signal transduction and targeted therapy · 2022Trial
- Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2016Trial
- Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck.Annals of oncology : official journal of the European Society for Medical Oncology · 2013Trial
- Trial
- The Managed Acquisition of Chemoresistance as an Informative Tool for Tumor Research.International journal of molecular sciences · 2025Review
- Antibody dependent cell-mediated cytotoxicity selection pressure induces diverse mechanisms of resistance.Cancer biology & therapy · 2023Article
- Microphysiological head and neck cancer model identifies novel role of lymphatically secreted monocyte migration inhibitory factor in cancer cell migration and metabolism.Biomaterials · 2023Article
- Comprehensive Molecular Landscape of Cetuximab Resistance in Head and Neck Cancer Cell Lines.Cells · 2022Article
- Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer.International journal of molecular sciences · 2021Article
- EGFR Alterations Influence the Cetuximab Treatment Response and c-MET Tyrosine-Kinase Inhibitor Sensitivity in Experimental Head and Neck Squamous Cell Carcinomas.Pathology oncology research : POR · 2021Article
- Monoclonal Antibodies in Cancer Therapy.Antibodies (Basel, Switzerland) · 2020Review
- Improving the Efficacy of Tumor Radiosensitization Through Combined Molecular Targeting.Frontiers in oncology · 2020Review
- MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma.Scientific reports · 2019Article
- Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma.Molecular pharmacology · 2019Article
- Lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment: A case report.Oncology letters · 2018Article
- Combining Chk1/2 Inhibition with Cetuximab and Radiation EnhancesMolecular cancer therapeutics · 2017Article
- RETRACTED: The receptor tyrosine kinase AXL mediates nuclear translocation of the epidermal growth factor receptor.Science signaling · 2017Article
- Targeted therapy combined with radiotherapy in non-small-cell lung cancer: a review of the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2017Review
- A humanized chimeric antibody Hai178 targeted to the β subunit of F1F0 ATP synthase.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe epidermal growth factor receptor (EGFR) is recognized as a key mediator of proliferation and progression in many human tumors. A series of EGFR-specific inhibitors have recently gained Food and Drug Administration approval in oncology. These strategies of EGFR inhibition have shown major tumor regressions in approximately 10% to 20% of advanced cancer patients. Many tumors, however, eventually manifest resistance to treatment. Efforts to better understand the underlying mechanisms of acquired resistance to EGFR inhibitors, and potential strategies to overcome resistance, are greatly needed. EXPERIMENTAL
designTo develop cell lines with acquired resistance to EGFR inhibitors we utilized the human head and neck squamous cell carcinoma tumor cell line SCC-1. Cells were treated with increasing concentrations of cetuximab, gefitinib, or erlotinib, and characterized for the molecular changes in the EGFR inhibitor-resistant lines relative to the EGFR inhibitor-sensitive lines.
resultsEGFR inhibitor-resistant lines were able to maintain their resistant phenotype in both drug-free medium and in athymic nude mouse xenografts. In addition, EGFR inhibitor-resistant lines showed a markedly increased proliferation rate. EGFR inhibitor-resistant lines had elevated levels of phosphorylated EGFR, mitogen-activated protein kinase, AKT, and signal transducer and activator of transcription 3, which were associated with reduced apoptotic capacity. Subsequent in vivo experiments indicated enhanced angiogenic potential in EGFR inhibitor-resistant lines. Finally, EGFR inhibitor-resistant lines showed cross-resistance to ionizing radiation.
conclusionsWe have developed EGFR inhibitor-resistant human head and neck squamous cell carcinoma cell lines. This model provides a valuable preclinical tool to investigate molecular mechanisms of acquired resistance to EGFR blockade.
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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.