Evidence map›Paper›PMID 27517839›Full record

ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2017

PTEN loss is associated with a poor response to trastuzumab in HER2-overexpressing gastroesophageal adenocarcinoma.

Yasunori Deguchi, Hiroshi Okabe, Nobu Oshima, Shigeo Hisamori, Sachiko Minamiguchi, Manabu Muto, Yoshiharu Sakai

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
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

32 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. COPS5 inhibition synergizes with the antitumor effect of trastuzumab by PTEN upregulation in HER2-amplified gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
    Article
  3. Review
  4. Review
  5. Article
  6. HER2-targeted therapies beyond breast cancer - an update.Nature reviews. Clinical oncology · 2024
    Review
  7. Review
  8. Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024
    Article
  9. Article
  10. Review
  11. Review
  12. Molecular mechanism of XB130 adaptor protein mediates trastuzumab resistance in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  13. Article
  14. Review
  15. Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022
    Review
  16. Current status and future perspectives in HER2 positive advanced gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
    Review
  17. Review
  18. Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: where do we stand?Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021
    Review
  19. Article
  20. Article
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

7 authors at 1 institution in 1 country.

Yasunori DeguchiDepartment of Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Hiroshi OkabeDepartment of Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. hokabe@kuhp.kyoto-u.ac.jp.
Nobu OshimaDepartment of Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Shigeo HisamoriDepartment of Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Sachiko MinamiguchiDepartment of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Manabu MutoDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yoshiharu SakaiDepartment of Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Kyoto University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough trastuzumab improves the outcome of patients with human epidermal growth factor receptor 2 (HER2)-overexpressing gastric or gastroesophageal junction adenocarcinoma (collectively referred to as "gastroesophageal adenocarcinoma"; GEA), no clinical response is observed in a substantial population of patients. A predictive biomarker of trastuzumab response is required. The aim of this study was to evaluate whether the hyperactivation of the downstream phosphatidylinositol 3-kinase pathway, due to phosphatase and tensin homolog (PTEN) loss or PIK3CA mutations, could provide trastuzumab resistance in GEA.

methodsExpression of HER2 and PTEN, and PIK3CA gene mutations were screened in 264 surgically resected GEA specimens. The effects of PTEN knockdown on the response to trastuzumab on cell viability, HER2 downstream signaling, apoptosis, and cell cycle were evaluated in HER2-overexpressing NCI-N87 gastric adenocarcinoma and OE19 esophageal adenocarcinoma cell lines. Inhibition of xenograft tumor growth by trastuzumab was investigated in OE19 cells with or without PTEN knockdown. The PTEN expression and objective response were analyzed in 23 GEA patients who received trastuzumab-based therapy.

resultsPTEN loss was identified in 34.5 % of HER2-overexpressing GEA patients, whereas PIK3CA mutations were rare (5.6 %). Trastuzumab-mediated growth suppression, apoptosis, and G

conclusionsPTEN loss was frequently found in HER2-overexpressing tumors, and was associated with a poor response to trastuzumab-based therapy in patients with GEA.

Indexed as

AdenocarcinomaAgedAged, 80 and overAnimalsCell Line, TumorClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesEsophageal NeoplasmsFemaleHumansMaleMice, NudeMiddle AgedMutationPhosphatidylinositol 3-KinasesClass I Phosphatidylinositol 3-KinasesERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesPhosphatidylinositol 3-KinasesPIK3CA protein, humanPTEN PhosphohydrolasePTEN protein, humanTrastuzumabEsophageal adenocarcinomaGastric adenocarcinomaHuman epidermal growth factor receptor 2Phosphatase and tensin homologTrastuzumab

Identifiers

PMID27517839
OpenAlexW2516542059

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Registered trials

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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.