ArticleCancer science2018
Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer.
Article in Cancer science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Investigation of the antitumor activity of lapatinib and NNC 55-0396 dihydrochloride combination in gastric adenocarcinoma.Medical oncology (Northwood, London, England) · 2025Article
- The Histone Deacetylase Inhibitor Entinostat Mediates HER2 Downregulation in Gastric Cancer, Providing the Basis for Its Particular Efficacy in HER2-Amplified Tumors and in Combination Therapies.Cancer research and treatment · 2025Article
- Advances in the treatment of human epidermal growth factor receptor 2-positive gastric cancer.International journal of clinical oncology · 2024Review
- Vorinostat Treatment of Gastric Cancer Cells Leads to ROS-Induced Cell Inhibition and a Complex Pattern of Molecular Alterations in Nrf2-Dependent Genes.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Applications of Modified Mesenchymal Stem Cells as Targeted Systems against Tumor Cells.International journal of molecular sciences · 2024Review
- Proteome-based molecular subtyping and therapeutic target prediction in gastric cancer.Molecular oncology · 2024Article
- The Combination of Afatinib With Dasatinib or Miransertib Results in Synergistic Growth Inhibition of Stomach Cancer Cells.World journal of oncology · 2024Article
- Novel Biomarkers of Gastric Cancer: Current Research and Future Perspectives.Journal of clinical medicine · 2023Review
- Overview of Chemotherapy for Gastric Cancer.Journal of clinical medicine · 2023Review
- Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers.Open life sciences · 2023Article
- Contribution of upregulated aminoacyl-tRNA biosynthesis to metabolic dysregulation in gastric cancer.Journal of gastroenterology and hepatology · 2021Article
- Amplification of the human epidermal growth factor receptor 2 (Journal of gastrointestinal oncology · 2021Article
- An analysis of HER2 amplification in cervical adenocarcinoma: correlation with clinical outcomes and the International Endocervical Adenocarcinoma Criteria and Classification.The journal of pathology. Clinical research · 2021Article
- Case Report: Durable Clinical Response to Third-Line Pyrotinib After Resistance to Trastuzumab in a Gastric Cancer Patient.Frontiers in oncology · 2021Article
- Review
- Slicing Spheroids in Microfluidic Devices for Morphological and Immunohistochemical Analysis.Micromachines · 2020Article
- Review
- Acquired resistance mechanisms to afatinib in HER2-amplified gastric cancer cells.Cancer science · 2019Article
- MET as resistance factor for afatinib therapy and motility driver in gastric cancer cells.PloS one · 2019Article
- HER4 expression in estrogen receptor-positive breast cancer is associated with decreased sensitivity to tamoxifen treatment and reduced overall survival of postmenopausal women.Breast cancer research : BCR · 2018Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-human epidermal growth factor receptor 2 (HER2) drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. First, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs. In the drug sensitivity analysis, both afatinib and neratinib produced an antitumor effect in most of the HER2-amplified cell lines. However, some cells were not sensitive to the drugs. When the molecular profiles of the cells were compared based on the drug sensitivities, we found that cancer cells with lower mRNA expression levels of IGFBP7, a tumor suppressor gene that inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R), were less sensitive to pan-HER inhibitors. A combination therapy consisting of pan-HER inhibitors and an IGF-1R inhibitor, picropodophyllin, showed a notable synergistic effect. Among 123 clinical samples, we found 19 cases of HER2 amplification and three cases of oncogenic mutations. In conclusion, afatinib and neratinib are promising therapeutic options for the treatment of HER2-amplified gastric cancer. In addition to HER2 amplification, IGFBP7 might be a biomarker of sensitivity to these drugs, and IGF-1R-targeting therapy can overcome drug insensitiveness in HER2-amplified gastric cancer.
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