ArticleOncogenesis2023
Exploring potential molecular resistance and clonal evolution in advanced HER2-positive gastric cancer under trastuzumab therapy.
Article in Oncogenesis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 18 citations in OpenAlex.
- Review
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Repurposing melatonin for its potential roles in gastrointestinal cancers: highlighting the molecular mechanisms.Cancer cell international · 2026Review
- Comprehensive characterization of MET exon 14 skipping mutations in non-small cell lung cancer.Respiratory research · 2026Article
- Glycolytic reprogramming in precancerous lesions of gastric cancer progression: pathogenesis and therapeutic potential.Frontiers in oncology · 2026Review
- Therapeutic misalignment averted by clonal evolutionary evidence: molecular confirmation of hepatic metastasis in SMARCA4-deficient non-small cell lung cancer initially misdiagnosed as resectable cholangiocarcinoma.Frontiers in oncology · 2026Article
- Molecular features influencing clinical outcome of advanced HER2-positive gastric cancer receiving trastuzumab plus chemotherapy.Annals of medicine · 2025Article
- Novel Resistance Mechanisms to Second-Generation EGFR Tyrosine Kinase Inhibitor Afatinib and Associations With Genomic Features in NSCLC.Genes, chromosomes & cancer · 2025Article
- Article
- Evolution of HER2-low expression from primary to paired metastatic gastric cancer lesions.NPJ precision oncology · 2025Article
- 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
- Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma.Journal of translational medicine · 2025Article
- Research advances in the molecular classification of gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Progress of PD-1/PD-L1 inhibitor combination therapy in immune treatment for HER2-positive tumors.European journal of clinical pharmacology · 2024Review
- HER2International journal of oncology · 2024Review
- Treatment strategies for patients with HER2-positive gastric cancer.Cancer biology & medicine · 2024Article
- Latin American young patients with gastric adenocarcinoma: worst prognosis and outcomes.Journal of gastrointestinal oncology · 2023Article
- Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2-positive gastric cancer (GC) makes up 15-20% of all GC incidences, and targeted therapy with trastuzumab is the standard of treatment. However, the mechanisms of resistance to trastuzumab are still not fully understood and presents a significant challenge in clinical practice. In this study, whole exome sequencing (WES) was performed on paired tumor tissues before trastuzumab treatment (at baseline) and at progressive disease (PD) in 23 GC patients. Clinicopathological and molecular features that may be associated with primary and/or acquired resistance to trastuzumab were identified. Lauren classification of intestinal type was associated with a more prolonged progression-free survival (PFS) than diffuse type (HR = 0.29, P = 0.019). Patients with low tumor mutation burden (TMB) showed significantly worse PFS, while high chromosome instability (CIN) was correlated with prolonged OS (HR = 0.27; P = 0.044). Patients who responded to treatment had a higher CIN than nonresponders, and a positive trend towards increasing CIN was observed as response improved (P = 0.019). In our cohort, the most common genes to acquire mutations are AURKA, MYC, STK11, and LRP6 with four patients each. We also discovered an association between clonal branching pattern and survival, with an extensive clonal branching pattern being more closely related to a shorter PFS than other branching patterns (HR = 4.71; P = 0.008). We identified potential molecular and clinical factors that provide insight regarding potential association to trastuzumab resistance in advanced HER2-positive GC patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.