ArticleJournal of cancer research and clinical oncology2023
KRAS mutation as a predictor of insufficient trastuzumab efficacy and poor prognosis in HER2-positive advanced gastric cancer.
Article in Journal of cancer research and clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 14 citations in OpenAlex.
- Clinical impact of intratumoral HER2 heterogeneity on trastuzumab deruxtecan efficacy in patients with HER2-positive gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Copy Number-Based Oncogene Dominance May Suggest ERBB2 Dependence and Trastuzumab Response in HER2-Positive Gastric Cancer.Targeted oncology · 2026Article
- HER2 and urothelial carcinoma: current understanding and future directions.Nature reviews. Urology · 2026Review
- Unlocking HER2 as a target in KRAS-mutated rectal cancer: a case of significant response to zanidatamab-based regimen.Frontiers in immunology · 2026Article
- Review
- Association of HER2 amplification or overexpression with overall survival in advanced upper gastrointestinal adenocarcinomas.BJC reports · 2025Article
- Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study.Signal transduction and targeted therapy · 2025Article
- The Combination of Afatinib With Dasatinib or Miransertib Results in Synergistic Growth Inhibition of Stomach Cancer Cells.World journal of oncology · 2024Article
- Comprehensive Multiomics Analyses Establish the Optimal Prognostic Model for Resectable Gastric Cancer : Prognosis Prediction for Resectable GC.Annals of surgical oncology · 2024Article
- The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression.Cancer medicine · 2023Article
- HER2 Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration.Journal of clinical medicine · 2023Review
- 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
- Fusobacterium Nucleatum-Induced Tumor Mutation Burden Predicts Poor Survival of Gastric Cancer Patients.Cancers · 2022Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAlthough RAS and PIK3CA mutations have been associated with resistance to anti-EGFR antibody in colorectal cancer or trastuzumab in breast cancer, their implications for trastuzumab resistance in HER2-positive advanced gastric cancer (AGC) remains unclear. We aimed to assess the relationship between trastuzumab efficacy and mutation status in the HER family signaling pathway.
methodsThis study retrospectively evaluated patients with HER2-positive AGC who received first-line trastuzumab-containing chemotherapy between March 2011 and November 2015. Multiplex genotyping, including KRAS, NRAS, PIK3CA, and BRAF, was then performed using the Luminex Assay, after which KRAS amplification was measured using quantitative real-time reverse transcription-polymerase chain reaction. Thereafter, the association between genetic alterations and clinical outcomes were evaluated.
resultsKRAS mutation (MT) was detected in 6 of 77 patients (7.8%), whereas KRAS amplification was found in 15 of 67 patients (22%). No mutations in NRAS, PIK3CA, or BRAF were identified. The KRAS MT group showed significantly worse response rates (16.7% vs. 66.2%, P = 0.016), progression-free survival [median, 4.8 vs. 11.6 months; hazard ratio (HR), 3.95; 95% CI, 1.60-9.76; P = 0.0029], and overall survival (11.5 vs. 23.6 months; HR, 3.80; 95% CI, 1.56-9.28; P = 0.033) compared to the KRAS wild-type group. KRAS amplification had no effect on clinical outcomes.
conclusionKRAS mutation was an independent prognostic factor for poor survival and might predict insufficient trastuzumab efficacy, whereas KRAS amplification showed no prognostic significance during trastuzumab treatment. Further investigations are warranted to confirm the predictive value of KRAS status in HER2-positive AGC.
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