ArticleBritish journal of cancer2014
HER2, MET and FGFR2 oncogenic driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Pooled it
- A phase II study of cabozantinib and pembrolizumab in advanced gastric/gastroesophageal adenocarcinomas resistant or refractory to immune checkpoint inhibitors.The oncologist · 2024Trial
- Molecular effects of Lapatinib in the treatment of HER2 overexpressing oesophago-gastric adenocarcinoma.British journal of cancer · 2015Trial
- Spatial heterogeneity of FGFR2b in gastric cancer: a comparative analysis of primary tumors and peritoneal dissemination.Virchows Archiv : an international journal of pathology · 2026Article
- Biology before stage in advanced gastric cancer: converting to cure in biomarker-selected patients.Journal of gastrointestinal oncology · 2026Article
- A Bioinformatics-Driven ceRNA Network in Stomach Adenocarcinoma: Identification of Novel Prognostic mRNA-miRNA-lncRNA Interactions.Medical sciences (Basel, Switzerland) · 2025Article
- The Receptor Tyrosine Kinase Axl in (Advanced) Gastric Cancer-From Pathophysiology to Therapeutic Impact.Medicina (Kaunas, Lithuania) · 2025Review
- Theranostic Approaches for Gastric Cancer: An Overview of In Vitro and In Vivo Investigations.Cancers · 2024Review
- Deciphering the FGFR2 Code: Innovative Targets in Gastric Cancer Therapy.Current oncology (Toronto, Ont.) · 2024Review
- Futibatinib, an Irreversible FGFR1-4 Inhibitor for the Treatment of FGFR-Aberrant Tumors.The oncologist · 2023Review
- Targeted therapy for multiple gene mutations in multiple metastases of advanced gastric cancer: a case report.Frontiers in oncology · 2023Article
- Hepatocyte Growth Factor Enhances Antineoplastic Effect of 5-Fluorouracil by Increasing UPP1 Expression in HepG2 Cells.International journal of molecular sciences · 2022Article
- Review
- Transferrin receptor 1 promotes the fibroblast growth factor receptor-mediated oncogenic potential of diffused-type gastric cancer.Oncogene · 2022Article
- Targeting FGFR2 Positive Gastroesophageal Cancer: Current and Clinical Developments.OncoTargets and therapy · 2022Review
- The Relationship Between D-dimer and Prognosis in the Patients with Serum Alpha-Fetoprotein-Positive Gastric Cancer: A Retrospective Cohort Study.Clinical Medicine Insights. Oncology · 2022Article
- The beginning of the era of precision medicine for gastric cancer with fibroblast growth factor receptor 2 aberration.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Review
- Harnessing biomarkers of response to improve therapy selection in esophago-gastric adenocarcinoma.Pharmacogenomics · 2021Review
- Quantitation of ligand is critical for ligand-dependent MET signalling activation and determines MET-targeted therapeutic response in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Article
- Clinical difference between fibroblast growth factor receptor 2 subclass, type IIIb and type IIIc, in gastric cancer.Scientific reports · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGastric cancer (GC) is a leading cause of cancer deaths worldwide. Since the approval of trastuzumab, targeted therapies are emerging as promising treatment options for the disease. This study aimed to explore the molecular segmentation of several known therapeutics targets, human epidermal growth factor receptor 2 (HER2), MET and fibroblast growth factor receptor 2 (FGFR2), within GC using clinically approved or investigational kits and scoring criteria. Knowledge of how these markers are segmented in the same cohort of GC patients could improve future clinical trial designs.
methodsUsing immunohistochemistry (IHC) and FISH methods, overexpression and amplification of HER2, FGFR2 and MET were profiled in a cohort of Chinese GC samples. The correlations between anti-tumour sensitivity and the molecular segments of HER2, MET and FGFR2 alterations were further tested in a panel of GC cell lines and the patient-derived GC xenograft (PDGCX) model using the targeted inhibitors.
resultsOf 172 GC patients, positivity for HER2, MET and FGFR2 alternations was found in 23 (13.4%), 21 (12.2%) and 9 (5.2%) patients, respectively. Positivity for MET was found in 3 of 23 HER2-positive GC patients. Co-positivity for FGFR2 and MET was found in 1 GC patient, and amplification of the two genes was found in different tumour cells. Our study in a panel of GC cell lines showed that in most cell lines, amplification or high expression of a particular molecular marker was mutually exclusive and in vitro sensitivity to the targeted agents lapatinib, PD173074 and crizotinib was only observed in cell lines with the corresponding high expression of the drugs' target protein. SGC031, an MET-positive PDGCX mouse model, responded to crizotinib but not to lapatinib or PD173074.
conclusionsHuman epidermal growth factor receptor 2, MET and FGFR2 oncogenic driver alterations (gene amplification and overexpression) occur in three largely distinct molecular segments in GC. A significant proportion of HER2-negative patients may potentially benefit from MET- or FGFR2-targeted therapies.
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