ArticleNeoplasia (New York, N.Y.)2012
In pancreatic carcinoma, dual EGFR/HER2 targeting with cetuximab/trastuzumab is more effective than treatment with trastuzumab/erlotinib or lapatinib alone: implication of receptors' down-regulation and dimers' disruption.
Article in Neoplasia (New York, N.Y.), 2012. 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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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
40 citing papers in PubMed, 68 citations in OpenAlex.
- Trial
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- Maximizing activity and selectivity of antibody-mediated effector functions using antibody mixtures.mAbs · 2025Article
- Quantitative evaluation of trastuzumab deruxtecan pharmacokinetics and pharmacodynamics in mouse models of varying degrees of HER2 expression.CPT: pharmacometrics & systems pharmacology · 2024Article
- Advances and Prospects in the Treatment of Pancreatic Cancer.International journal of nanomedicine · 2023Review
- Design and selection of optimal ErbB-targeting bispecific antibodies in pancreatic cancer.Frontiers in immunology · 2023Article
- Biologic Evaluation of a Heterodimeric HER2-Albumin Targeted Affibody Molecule Produced by Chemo-Enzymatic Peptide Synthesis.Pharmaceutics · 2022Article
- Development of Dual Receptor Enhanced Pre-Targeting Strategy-A Novel Promising Technology for Immuno-Positron Emission Tomography Imaging.Advanced therapeutics · 2021Article
- Review
- Modeling pancreatic cancer in mice for experimental therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Proteogenomic analysis of pancreatic cancer subtypes.PloS one · 2021Article
- Prevalence, prognosis and predictive status of HER2 amplification in anti-EGFR-resistant metastatic colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget's disease.Journal of cancer research and clinical oncology · 2019Article
- Purified human anti-Tn and anti-T antibodies specifically recognize carcinoma tissues.Scientific reports · 2019Article
- Article
- ErbB2 Targeted Epigenetic Modulation: Anti-tumor Efficacy of the ADC Trastuzumab-HDACi ST8176AA1.Frontiers in oncology · 2019Article
- Epidermal growth factor receptor peptide vaccination induces cross-reactive immunity to human EGFR, HER2, and HER3.Cancer immunology, immunotherapy : CII · 2018Article
- Emerging trends in the immunotherapy of pancreatic cancer.Cancer letters · 2018Review
- Stromal mesenchymal stem cells facilitate pancreatic cancer progression by regulating specific secretory molecules through mutual cellular interaction.Journal of Cancer · 2018Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously demonstrated the synergistic therapeutic effect of the cetuximab (anti-epidermal growth factor receptor [EGFR] monoclonal antibody, mAb)-trastuzumab (anti-HER2 mAb) combination (2mAbs therapy) in HER2(low) human pancreatic carcinoma xenografts. Here, we compared the 2mAbs therapy, the erlotinib (EGFR tyrosine kinase inhibitor [TKI])-trastuzumab combination and lapatinib alone (dual HER2/EGFR TKI) and explored their possible mechanisms of action. The effects on tumor growth and animal survival of the three therapies were assessed in nude mice xenografted with the human pancreatic carcinoma cell lines Capan-1 and BxPC-3. After therapy, EGFR and HER2 expression and AKT phosphorylation in tumor cells were analyzed by Western blot analysis. EGFR/HER2 heterodimerization was quantified in BxPC-3 cells by time-resolved FRET. In K-ras-mutated Capan-1 xenografts, the 2mAbs therapy gave significantly higher inhibition of tumor growth than the erlotinib/trastuzumab combination, whereas in BxPC-3 (wild-type K-ras) xenografts, the erlotinib/trastuzumab combination showed similar growth inhibition but fewer tumor-free mice. Lapatinib showed no antitumor effect in both types of xenografts. The efficacy of the 2mAbs therapy was partly Fc-independent because F(ab')(2) fragments of the two mAbs significantly inhibited BxPC-3 growth, although with a time-limited therapeutic effect. The 2mAbs therapy was associated with a reduction of EGFR and HER2 expression and AKT phosphorylation. BxPC-3 cells preincubated with the two mAbs showed 50% less EGFR/HER2 heterodimers than controls. In pancreatic carcinoma xenografts, the 2mAbs therapy is more effective than treatments involving dual EGFR/HER2 TKIs. The mechanism of action may involve decreased AKT phosphorylation and/or disruption of EGFR/HER2 heterodimerization.
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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.