Evidence map›Paper›PMID 41832911›Full record

ArticleTargeted oncology2026

Copy Number-Based Oncogene Dominance May Suggest ERBB2 Dependence and Trastuzumab Response in HER2-Positive Gastric Cancer.

Takeru Wakatsuki, Noriko Yamamoto, Naoki Ishizuka, Shuichi Hironaka, Keiko Minashi, Shigenori Kadowaki, Hidekazu Hirano, Hirokazu Shoji, Toshifumi Yamaguchi, Keisho Chin and 8 more

Abstract read
In one paragraph

Article in Targeted oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Takeru WakatsukiDepartment of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. takeru.wakatsuki@jfcr.or.jp.ORCID http://orcid.org/0000-0002-1463-3859
Noriko YamamotoDivision of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Naoki IshizukaCenter for Digital Transformation of Healthcare Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0002-5856-9668
Shuichi HironakaDepartment of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.ORCID http://orcid.org/0000-0001-9714-231X
Keiko MinashiClinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
Shigenori KadowakiDepartment of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.ORCID http://orcid.org/0000-0001-9923-5309
Hidekazu HiranoDepartment of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.ORCID http://orcid.org/0000-0003-1343-1419
Hirokazu ShojiDepartment of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.ORCID http://orcid.org/0000-0002-8922-5227
Toshifumi YamaguchiCancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan.ORCID http://orcid.org/0000-0003-1399-1918
Keisho ChinDepartment of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.ORCID http://orcid.org/0000-0002-2015-8185
Mariko OguraDepartment of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.ORCID http://orcid.org/0000-0002-1004-8425
Izuma NakayamaDepartment of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.ORCID http://orcid.org/0000-0003-4987-1934
Hiroki OsumiDepartment of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.ORCID http://orcid.org/0000-0002-4742-0446
Arisa UekiDepartment of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.ORCID http://orcid.org/0000-0001-9205-5452
Shigehisa KitanoDepartment of Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.ORCID http://orcid.org/0000-0002-4041-8298
Narikazu BokuDepartment of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-1438-707X
Kensei YamaguchiDepartment of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.ORCID http://orcid.org/0000-0001-6887-5709
Daisuke TakahariDepartment of Gastrointestinal Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.ORCID http://orcid.org/0000-0002-2492-6014

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhile oncogene co-amplification is frequently observed, its clinical significance remains unclear, particularly with regard to its association with copy number.

objectiveThe aim of this study was to elucidate the molecular traits of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, focusing on copy numbers of ERBB2 and other oncogenes, and to investigate their association with treatment efficacy.

methodsThis is a collaborative study associated with the HIGHSOX trial investigating the efficacy of trastuzumab combined with S-1 and oxaliplatin in HER2-positive gastric cancer, and next-generation sequencing was performed. Tumors in which ERBB2 was the highest copy number among co-amplified oncogenes were defined as "ERBB2 dominant". The others were defined as "non-ERBB2 dominant".

resultsA total of 32 patients were enrolled, and the median progression-free survival and overall survival were 11.8 and 28.8 months, respectively. ERBB2 amplification was present in 84.4%, with the majority (88%) exhibiting either co-amplification of ERBB2 with other oncogenes (75%) or amplification of other oncogenes alone (13%), including KRAS, MET, FGFR2, and CCNE1. A potential inverse relationship in copy number between ERBB2 and other oncogenes (ρ = - 0.345, p = 0.058) was observed. The ERBB2 copy number was significantly higher than that of other oncogenes in ERBB2-dominant tumors, whereas the opposite pattern was observed in non-ERBB2-dominant tumors (both p < 0.001). Non-ERBB2-dominant tumors showed significantly shorter progression-free survival (median progression-free survival: 6.9 vs 17.0 months, hazard ratio, 6.40, p = 0.001), overall survival (median overall survival 14.8 vs 35.5 months, hazard ratio, 2.72, p = 0.016), and a numerically lower response rate (63.6% vs 90.0%, p = 0.151).

conclusionsCopy number-based oncogene dominance may suggest tumor dependence and response to HER2-targeted therapy, highlighting a potential novel biomarker in HER2-positive gastric cancer.

Indexed as

Erb-b2 Receptor Tyrosine KinasesStomach NeoplasmsTrastuzumabAdultAgedDNA Copy Number VariationsFemaleGene DosageHumansMaleMiddle AgedERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesTrastuzumab

Identifiers

PMID41832911
PMCPMC13031244

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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.