ArticleScientific reports2023
Novel HER2-targeted therapy to overcome trastuzumab resistance in HER2-amplified gastric cancer.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Efficacy and safety of trastuzumab deruxtecan in gastrointestinal malignancies: a systemic review and meta-analysis.Frontiers in gastroenterology (Lausanne, Switzerland) · 2025Pooled it
- Review
- A biparatopic HER2-targeting ADC constructedRSC chemical biology · 2025Article
- Lapatinib-Resistant HER2+ Breast Cancer Cells Are Associated with Dysregulation of MAPK and p70S6K/PDCD4 Pathways and Calcium Management, Influence of Cryptotanshinone.International journal of molecular sciences · 2025Article
- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- Tumor-type agnostic, targeted therapies make a new step forward: The first tumor-agnostic approval of a HER2-targeted therapy.Biomolecules & biomedicine · 2024Article
- HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments.Cancers · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trastuzumab is used to treat HER2-amplified metastatic gastric cancer; however, most patients become trastuzumab-resistant within a year. Knowledge of the mechanisms underlying trastuzumab resistance is required to overcome this limitation. Here, we aimed to elucidate this resistance mechanism using four trastuzumab-resistant (TR) cell lines and investigate the efficacy of HER2-targeted therapies to overcome treatment resistance. Each TR cell line had different phenotypic characteristics. Interestingly, HER2 expression remained as high as the parental cell lines in TR cell lines, suggesting that HER2-targeted agents were still useful. As expected, three tyrosine kinase inhibitors (lapatinib, neratinib, and tucatinib) and one antibody-drug conjugate (trastuzumab deruxtecan: T-DXd) exhibited good antitumor effects against TR cell lines. We further investigated the potential biological mechanism of T-DXd. When treated with trastuzumab or T-DXd, HER2 or its downstream signals were disrupted in parental cell lines, but not in TR cell lines. Moreover, T-DXd induced the expression of pH2A.X and cPARP and caused cell cycle arrest in the S or G2-M phase in TR cell lines. T-DXd showed promising antitumor activity in both parental and TR cell lines, suggesting that it is a potential candidate for overcoming trastuzumab resistance.
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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.