ArticleOncotarget2017
PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Pooled it
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Ulcerative colitis and colorectal cancer: Pathogenic insights and precision strategies for prevention and treatment.World journal of gastrointestinal oncology · 2025Review
- Human Epidermal Growth Factor Receptor 2 Positive Advanced Gastric or Esophagogastric Adenocarcinoma: Reflecting on the Past to Gain a New Insights.Current oncology reports · 2025Review
- Targeted Sequencing of HER2-Positive Breast Cancer Mutations Revealed a Potential Association between PIK3CA and Trastuzumab Resistance.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Establishment of a trastuzumab-resistant extramammary Paget disease model: loss of PTEN as a potential mechanism.British journal of cancer · 2024Article
- Review
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments.Cancers · 2024Review
- Genomic characterization between HER2-positive and negative gastric cancer patients in a prospective trial.Cancer medicine · 2023Article
- Molecular mechanism of XB130 adaptor protein mediates trastuzumab resistance in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Resistance to Trastuzumab.Cancers · 2022Review
- Poorly cohesive cells gastric carcinoma including signet-ring cell cancer: Updated review of definition, classification and therapeutic management.World journal of gastrointestinal oncology · 2022Review
- Current status and future perspectives in HER2 positive advanced gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Article
- Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: where do we stand?Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Review
- PTEN is a predictive biomarker of trastuzumab resistance and prognostic factor in HER2-overexpressing gastroesophageal adenocarcinoma.Scientific reports · 2021Article
- Amplification of the human epidermal growth factor receptor 2 (Journal of gastrointestinal oncology · 2021Article
- Article
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTrastuzumab is an active agent against human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). This study aimed to characterize resistance to trastuzumab-based front-line chemotherapy in HER2+ GC patients and to establish factors predictive of this resistance.
resultsAmong 129 HER2+ GC patients, 25% displayed rapid disease progression within 4 months from initiation of therapy. These patients showed a higher rate of signet ring cell histology, bone metastasis, poor performance status, frequent loss of PTEN expression, and low HER2 amplification index compared with patients who were progression-free for at least 4 months. In contrast, there was no significant difference in the frequency of the PIK3R1 variant. Multivariate analyses confirmed two independent molecular predictors for trastuzumab resistance: loss of PTEN expression and low HER2 amplification index (<5). Patients with one or both molecular predictors at diagnosis exhibited worse progression-free and overall survival compared to those without risk factors (
conclusionIn HER2+ GC patients, loss of PTEN expression and low HER2 AI correlated with resistance to trastuzumab-based therapy and dismal prognosis. Since patients harboring these molecular predictors are unlikely to respond to trastuzumab-based therapy, other novel therapeutic targets needed to be considered.
methodsHER2+ GC patients who were treated with trastuzumab in combination with either 5-fluorouracil/cisplatin or capecitabine/cisplatin were enrolled. Clinicopathologic features and molecular alterations of HER2, phosphoinositide 3-kinase regulatory subunit 1 (PIK3R1), and phosphatase and tensin homolog (PTEN) were correlated with treatment outcome. Factors predictive of resistance were also explored.
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