ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Dual kinase inhibition of EGFR and HER2 overcomes resistance to cetuximab in a novel in vivo model of acquired cetuximab resistance.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 93 citations in OpenAlex.
- An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer.Breast cancer research : BCR · 2021Trial
- Multi-drug inhibition of the HER pathway in metastatic colorectal cancer: results of a phase I study of pertuzumab plus cetuximab in cetuximab-refractory patients.Investigational new drugs · 2014Trial
- Targeting Folate Receptors for the Detection and Selective Treatment of Cancer: Advanced Precision Oncology in Practice.International journal of biological sciences · 2026Review
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- Novel Therapeutic Strategies for Squamous Cell Carcinoma of the Head and Neck: Beyond EGFR and Checkpoint Blockade.Biomedicines · 2025Review
- New clinical trial design in precision medicine: discovery, development and direction.Signal transduction and targeted therapy · 2024Review
- Targeted radionuclide therapy for head and neck squamous cell carcinoma: a review.Frontiers in oncology · 2024Review
- Establishment of head and neck squamous cell carcinoma mouse models for cetuximab resistance and sensitivity.Cancer drug resistance (Alhambra, Calif.) · 2023Article
- Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma.Journal of translational medicine · 2021Article
- Patient-derived xenograft (PDX) models of colorectal carcinoma (CRC) as a platform for chemosensitivity and biomarker analysis in personalized medicine.Neoplasia (New York, N.Y.) · 2021Article
- Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers.Frontiers in oncology · 2021Review
- Cytoplasmic Chaperones Enhance Soluble Expression of Anti-EGFR huscFv inIranian journal of biotechnology · 2020Article
- Combined targeting EGFR and SRC as a potential novel therapeutic approach for the treatment of triple negative breast cancer.Therapeutic advances in medical oncology · 2020Article
- Preferential Response of Basal-Like Head and Neck Squamous Cell Carcinoma Cell Lines to EGFR-Targeted Therapy Depending onCancers · 2019Article
- Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models.Targeted oncology · 2019Article
- Simultaneous targeting of EGFR, HER2, and HER4 by afatinib overcomes intrinsic and acquired cetuximab resistance in head and neck squamous cell carcinoma cell lines.Molecular oncology · 2018Article
- Enhanced tumor-targeting selectivity by modulating bispecific antibody binding affinity and format valence.Scientific reports · 2017Article
- Article
- Inhibition of proliferation and induction of apoptosis in RB116 retinoblastoma cells by afatinib treatment.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
purposeAcquired resistance to cetuximab, a chimeric epidermal growth factor receptor (EGFR)-targeting monoclonal antibody, is a widespread problem in the treatment of solid tumors. The paucity of preclinical models has limited investigations to determine the mechanism of acquired therapeutic resistance, thereby limiting the development of effective treatments. The purpose of this study was to generate cetuximab-resistant tumors in vivo to characterize mechanisms of acquired resistance. EXPERIMENTAL
designWe generated cetuximab-resistant clones from a cetuximab-sensitive bladder cancer cell line in vivo by exposing cetuximab-sensitive xenografts to increasing concentrations of cetuximab, followed by validation of the resistant phenotype in vivo and in vitro using invasion assays. A candidate-based approach was used to examine the role of HER2 on mediating cetuximab resistance both in vitro and in vivo.
resultsWe generated a novel model of cetuximab resistance, and, for the first time in the context of EGFR-inhibitor resistance, we identified increased phosphorylation of a C-terminal fragment of HER2 (611-CTF) in cetuximab-resistant cells. Afatinib (BIBW-2992), an irreversible kinase inhibitor targeting EGFR and HER2, successfully inhibited growth of the cetuximab-resistant cells in vitro. When afatinib was combined with cetuximab in vivo, we observed an additive growth inhibitory effect in cetuximab-resistant xenografts.
conclusionsThese data suggest that the use of dual EGFR-HER2 kinase inhibitors can enhance responses to cetuximab, perhaps in part due to downregulation of 611-CTF. This study conducted in a novel in vivo model provides a mechanistic rationale for ongoing phase I clinical trials using this combination treatment modality.
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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.