ArticleMolecular oncology2018
Effects of trastuzumab and afatinib on kinase activity in gastric cancer cell lines.
Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- The impact of the PI3K/AKT/mTOR signaling pathway on trastuzumab resistance in HER2-positive gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Prognostic value of RNA methylation-related genes in gastric adenocarcinoma based on bioinformatics.PeerJ · 2024Article
- Quantitative proteomics profiling reveals the inhibition of trastuzumab antitumor efficacy by phosphorylated RPS6 in gastric carcinoma.Cancer chemotherapy and pharmacology · 2023Article
- HER3 PET Imaging Predicts Response to Pan Receptor Tyrosine Kinase Inhibition Therapy in Gastric Cancer.Molecular imaging and biology · 2023Article
- Hyperpolarized [1-Molecular imaging and biology · 2022Article
- Article
- Metabolomic therapy response prediction in pretherapeutic tissue biopsies for trastuzumab in patients with HER2-positive advanced gastric cancer.Clinical and translational medicine · 2021Article
- The Significance of MET Expression and Strategies of Targeting MET Treatment in Advanced Gastric Cancer.Frontiers in oncology · 2021Article
- Determining the effects of trastuzumab, cetuximab and afatinib by phosphoprotein, gene expression and phenotypic analysis in gastric cancer cell lines.BMC cancer · 2020Article
- A novel anti-HER2 antibody GB235 reverses Trastuzumab resistance in HER2-expressing tumor cells in vitro and in vivo.Scientific reports · 2020Article
- Review
- Temporal Modulation of HER2 Membrane Availability Increases Pertuzumab Uptake and Pretargeted Molecular Imaging of Gastric Tumors.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Article
- Targeted and novel therapy in advanced gastric cancer.Experimental hematology & oncology · 2019Review
- MET as resistance factor for afatinib therapy and motility driver in gastric cancer cells.PloS one · 2019Article
- Caveolin-1 mediates cellular distribution of HER2 and affects trastuzumab binding and therapeutic efficacy.Nature communications · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanism of action of the HER2-targeted antibody trastuzumab is only partially understood, and the direct effects of trastuzumab on the gastric cancer signaling network are unknown. In this study, we compared the molecular effect of trastuzumab and the HER kinase inhibitor afatinib on the receptor tyrosine kinase (RTK) network and the downstream-acting intracellular kinases in gastric cancer cell lines. The molecular effects of trastuzumab and afatinib on the phosphorylation of 49 RTKs and 43 intracellular kinase phosphorylation sites were investigated in three gastric cancer cell lines (NCI-N87, MKN1, and MKN7) using proteome profiling. To evaluate these effects, data were analyzed using mixed models and clustering. Moreover, proliferation assays were performed. Our comprehensive quantitative analysis of kinase activity in gastric cancer cell lines indicates that trastuzumab and afatinib selectively influenced the HER family RTKs. The effects of trastuzumab differed between cell lines, depending on the presence of activated HER2. The effects of trastuzumab monotherapy were not transduced to the intracellular kinase network. Afatinib alone or in combination with trastuzumab influenced HER kinases in all cell lines; that is, the effects of monotherapy and combination therapy were transduced to the intracellular kinase network. These results were confirmed by proliferation analysis. Additionally, the MET-amplified cell line Hs746T was identified as afatinib nonresponder. The dependence of the effect of trastuzumab on the presence of activated HER2 might explain the clinical nonresponse of some patients who are routinely tested for HER2 expression and gene amplification in the clinic but not for HER2 activation. The consistent effects of afatinib on HER RTKs and downstream kinase activation suggest that afatinib might be an effective candidate in the future treatment of patients with gastric cancer irrespective of the presence of activated HER2. However, MET amplification should be taken into account as potential resistance factor.
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