ArticleClinical cancer research : an official journal of the American Association for Cancer Research2017
HER3 Targeting Sensitizes HNSCC to Cetuximab by Reducing HER3 Activity and HER2/HER3 Dimerization: Evidence from Cell Line and Patient-Derived Xenograft Models.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Resistance Mechanisms in Immunotherapy-Radiotherapy/Chemotherapy Combinations in Locally Advanced Head & Neck Squamous Cell Carcinoma.Oncology research · 2026Review
- [Research progress on the mechanisms of resistance to cetuximab targeted therapy in head and neck squamous cell carcinoma].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Feasibility Assessment of Autologous Human Immune System (HIS) ImmunoGraft Platform Development Using Autologous Mobilized Peripheral Blood (MPB) CD34 Cells Derived from Adult HNSCC Patient.International journal of molecular sciences · 2025Article
- Spatial Transcriptomic Analysis of Surgical Resection Specimens of Primary Head and Neck Squamous Cell Carcinoma Treated with Afatinib in a Window-of-Opportunity Study (EORTC90111-24111).International journal of molecular sciences · 2025Article
- Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics.Cancers · 2025Review
- New clinical trial design in precision medicine: discovery, development and direction.Signal transduction and targeted therapy · 2024Review
- Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives.International journal of molecular sciences · 2024Review
- ESM1 facilitates the EGFR/HER3-triggered epithelial-to-mesenchymal transition and progression of gastric cancer via modulating interplay between Akt and angiopoietin-2 signaling.International journal of biological sciences · 2024Article
- Targeting ST8SIA6-AS1 counteracts KRASExperimental hematology & oncology · 2023Article
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
- SLC12A5 promotes hepatocellular carcinoma growth and ferroptosis resistance by inducing ER stress and cystine transport changes.Cancer medicine · 2023Article
- HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022Review
- Targeting HER3-dependent activation of nuclear AKT improves radiotherapy of non-small cell lung cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2022Article
- 3D cell culture alters signal transduction and drug response in head and neck squamous cell carcinoma.Oncology letters · 2022Article
- Phase II Trial of CDX-3379 and Cetuximab in Recurrent/Metastatic, HPV-Negative, Cetuximab-Resistant Head and Neck Cancer.Cancers · 2022Article
- AXL regulates neuregulin1 expression leading to cetuximab resistance in head and neck cancer.BMC cancer · 2022Article
- Engaging innate immunity for targeting the epidermal growth factor receptor: Therapeutic options leveraging innate immunity versus adaptive immunity versus inhibition of signaling.Frontiers in oncology · 2022Review
- The Proteomic Landscape of Growth Factor Signaling Networks Associated withCancer research · 2021Article
- Anti‑HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma.Oncology reports · 2021Article
- Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer.Nature communications · 2021Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
purposeOur previous work suggested that HER3 inhibition sensitizes head and neck squamous cell carcinoma (HNSCC) to EGFR inhibition with cetuximab. This study aimed to define the role of HER3 in cetuximab resistance and the antitumor mechanisms of EGFR/HER3 dual targeting in HNSCC. EXPERIMENTAL
designWe treated cetuximab-resistant HNSCC UMSCC1-C and parental UMSCC1-P cell lines with anti-EGFR antibody cetuximab, anti-HER3 antibody MM-121, and their combination. We assessed activities of HER2, HER3, and downstream signaling pathways by Western blotting and cell growth by sulforhodamine B (SRB) and colony formation assays. HER3-specific shRNA was used to confirm the role of HER3 in cetuximab response. The combined efficacy and alterations in biomarkers were evaluated in UMSCC1-C xenograft and patient-derived xenograft (PDX) models.
resultsCetuximab treatment induced HER3 activation and HER2/HER3 dimerization in HNSCC cell lines. Combined treatment with cetuximab and MM-121 blocked EGFR and HER3 activities and inhibited the PI3K/AKT and ERK signaling pathways and HNSCC cell growth more effectively than each antibody alone. HER3 knockdown reduced HER2 activation and resensitized cells to cetuximab. Cetuximab-resistant xenografts and PDX models revealed greater efficacy of dual EGFR and HER3 inhibition compared with single antibodies. In PDX tissue samples, cetuximab induced HER3 expression and MM-121 reduced AKT activity.
conclusionsClinically relevant PDX models demonstrate that dual targeting of EGFR and HER3 is superior to EGFR targeting alone in HNSCC. Our study illustrates the upregulation of HER3 by cetuximab as one mechanism underlying resistance to EGFR inhibition in HNSCC, supporting further clinical investigations using multiple targeting strategies in patients who have failed cetuximab-based therapy. Clin Cancer Res; 23(3); 677-86. ©2016 AACR.
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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.