ArticleScientific reports2021
PTEN is a predictive biomarker of trastuzumab resistance and prognostic factor in HER2-overexpressing gastroesophageal adenocarcinoma.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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14 citing papers in PubMed, 14 citations in OpenAlex.
- mTORC2-NaChannels (Austin, Tex.) · 2026Article
- Current and Emerging Protein Biomarkers for the Diagnosis and Prognosis of Head and Neck Cancer.Genes · 2025Review
- COPS5 inhibition synergizes with the antitumor effect of trastuzumab by PTEN upregulation in HER2-amplified gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Diverse ERBB2/ERBB3 Activating Alterations and Coalterations Have Implications for HER2/3-Targeted Therapies across Solid Tumors.Cancer research communications · 2025Article
- Mechanisms of resistance to antibody-drug conjugates in cancer therapy: molecular basis and therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Star wars against leukemia: attacking the clones.Leukemia · 2024Review
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- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
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- Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential.Breast cancer : basic and clinical research · 2024Article
- Case report: Pyrotinib and tegafur combined with radiotherapy achieved notable response in HER2-amplified rectal cancer with multiple metastases after multiline treatments.Frontiers in pharmacology · 2024Article
- Genomic characterization between HER2-positive and negative gastric cancer patients in a prospective trial.Cancer medicine · 2023Article
- The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy.Therapeutic advances in medical oncology · 2023Article
- Resistance to Trastuzumab.Cancers · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poor trastuzumab (Tmab) response of patients with human epidermal growth factor receptor 2-overexpressing gastric or gastroesophageal junction adenocarcinoma (HER2-GEA) is associated with the inhibition of phosphatase and tensin homolog (PTEN) expression. In this multicenter, retrospective observational study, pathological samples of patients with HER2-GEA receiving Tmab-combined chemotherapy were immunohistochemically analyzed for PTEN expression. The primary endpoints were disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). We assessed the effect of conventional chemotherapy and Tmab alone or combined with PI3K pathway inhibitors in vitro in HER2-GEA cells with or without PTEN expression. Twenty-nine and 116 patients were in the PTEN-loss and PTEN-positive groups, respectively. In patients with the target region, DCR was significantly lower in PTEN-loss patients than in PTEN-positive patients (67% and 87%, respectively, p = 0.049). The multivariate analysis demonstrated that PTEN loss was significantly associated with shorter PFS (HR = 1.63, p = 0.035) and OS (HR = 1.83, p = 0.022). PTEN knockdown did not affect the cytostatic effect of 5-FU and cisplatin, whereas Tmab combined with the PI3K/mTOR inhibitor NPV-BEZ235 suppressed PTEN-knockdown cell proliferation. In patients with HER2-GEA, PTEN loss is a predictive biomarker of Tmab resistance and prognostic factor. Molecular-targeted therapy with a PI3K/mTOR inhibitor would be effective for HER2-GEA with PTEN loss.
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