ArticleThe oncologist2018
Genomic Profiling of HER2-Positive Gastric Cancer: PI3K/Akt/mTOR Pathway as Predictor of Outcomes in HER2-Positive Advanced Gastric Cancer Treated with Trastuzumab.
Article in The oncologist, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Global updates in the treatment of gastric cancer: a systematic review. Part 1: staging, classification and surgical treatment.Updates in surgery · 2020Pooled it
- Trial
- Gastric Cancer Organoids: Mechanistic Insights, Drug Discovery, and Translational Advances in Precision Medicine.Journal of gastric cancer · 2026Review
- 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
- 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
- Liqi Huatan Huoxue Formula Rescued Myocardial Cell Apoptosis of Coronary Microvascular Dysfunction Rat by Inhibiting Endogenous Apoptosis Pathway.Iranian journal of biotechnology · 2026Article
- Copy Number-Based Oncogene Dominance May Suggest ERBB2 Dependence and Trastuzumab Response in HER2-Positive Gastric Cancer.Targeted oncology · 2026Article
- Hippo-YAP/TAZ signaling in gastric cancer: molecular pathogenesis and emerging therapeutic horizons.Medical oncology (Northwood, London, England) · 2026Review
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- Precision treatment of gastrointestinal tumours and liver disease interaction mechanisms based on multi-omics data and microbiome hubs.Frontiers in cellular and infection microbiology · 2026Review
- Next-generation sequencing identifies potential mechanisms of primary resistance to trastuzumab-containing therapies in HER2-positive gastric cancer: Analysis based on real-world data and online databases.Human vaccines & immunotherapeutics · 2025Article
- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- Jian Pi Hua Tan Fang Reverses Trastuzumab Resistance of HER2-Positive Gastric Cancer Through PI3K/AKT/mTOR Pathway: Integrating Network Pharmacology, Molecular Docking and Experimental Validation.Immunity, inflammation and disease · 2025Article
- The Therapeutic Potential of Targeting Tumor Microenvironment and Modulation of Immunotherapy in Gastrointestinal Cancer.Current cancer drug targets · 2025Review
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Clinical application of targeted tumour sequencing tests for detecting ERBB2 amplification and optimizing anti-HER2 therapy in gastric cancer.BMC cancer · 2024Article
- A Review on Anaplastic Lymphoma Kinase (ALK) Rearrangements and Mutations: Implications for Gastric Carcinogenesis and Target Therapy.Current protein & peptide science · 2024Review
- Quantitative proteomics profiling reveals the inhibition of trastuzumab antitumor efficacy by phosphorylated RPS6 in gastric carcinoma.Cancer chemotherapy and pharmacology · 2023Article
- p70S6K/Akt dual inhibitor DIACC3010 is efficacious in preclinical models of gastric cancer alone and in combination with trastuzumab.Scientific reports · 2023Article
- Genomic characterization between HER2-positive and negative gastric cancer patients in a prospective trial.Cancer medicine · 2023Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHER2-positive gastric cancer (GC) affects 7%-34% of patients with GC. Trastuzumab-based first-line treatment has become the standard of care for HER2-positive advanced gastric cancer (AGC). However, there are no clinically validated biomarkers for resistance to HER2-targeted therapies. Upregulation of PI3K pathway and tyrosine kinase receptor (TKR) alterations have been noted as molecular mechanisms of resistance in breast cancer. Our study aimed to perform a molecular characterization of HER2-positive AGC and investigate the role of PI3K/Akt/mTOR signaling pathway activation and TKR gene copy number (GCN) gains as predictive biomarkers in HER2-positive AGC treated with trastuzumab. PATIENTS AND
methodsForty-two HER2-positive GC samples from patients treated with trastuzumab-based first-line chemotherapy were selected. DNA samples were sequenced. PTEN and MET immunohistochemistry were also performed.
resultsConcurrent genetic alterations were detected in 97.1% of HER2-positive AGC. We found activation of PI3K/Akt/mTOR pathway in 52.4% of patients and TKR GCN gains in 38.1%. TKR GCN gains did not correlate with overall survival (OS) or progression-free survival (PFS). Multivariate Cox models showed that PI3K/Akt/mTOR activation negatively affects the effectiveness of trastuzumab-based chemotherapy in terms of OS and PFS.
conclusionOur results provide for the first time a detailed molecular profile of concurrent genetic alterations in HER2-positive AGC. PI3K pathway activation could be used as a predictive marker of worse outcome in this patient population. In addition, gains in copy number of other TKR genes in this subgroup may also influence the survival benefit obtained with trastuzumab. IMPLICATIONS FOR PRACTICE: This article reports, for the first time, a detailed molecular profile of genomic alterations in patients with HER2-positive advanced gastric cancer (AGC). PI3K/Akt/mTOR signaling pathway activation seems to have a differentially negative effect on overall survival and progression-free survival in AGC treated with trastuzumab-based chemotherapy. Combining different targeted agents could be a successful therapeutic strategy to improve the prognosis of HER2-positive AGC.
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