ArticleOncotarget2017
Quantitative proteomics profiling reveals activation of mTOR pathway in trastuzumab resistance.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- The impact of the PI3K/AKT/mTOR signaling pathway on trastuzumab resistance in HER2-positive gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Identification of factors conferring resistance to trastuzumab deruxtecan in advanced gastric cancer: a translational study from the single-arm, phase II, DESTINY-Gastric06 trial.Precision clinical medicine · 2026Article
- Review
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments.Cancers · 2024Review
- Bioinformatics and Experimental Validation for Identifying Biomarkers Associated with AMG510 (Sotorasib) Resistance in KRASInternational journal of molecular sciences · 2024Article
- A proteomic landscape of pharmacologic perturbations for functional relevance.Journal of pharmaceutical analysis · 2024Article
- Comprehensive analysis of CPNE1 predicts prognosis and drug resistance in gastric adenocarcinoma.American journal of translational research · 2024Article
- Quantitative proteomics profiling reveals the inhibition of trastuzumab antitumor efficacy by phosphorylated RPS6 in gastric carcinoma.Cancer chemotherapy and pharmacology · 2023Article
- Synergistic Effects of Metformin and Trastuzumab on HER2 Positive Gastroesophageal Adenocarcinoma Cells In Vitro and In Vivo.Cancers · 2023Article
- Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway.International journal of molecular sciences · 2022Article
- Accum™ Technology: A Novel Conjugable Primer for Onco-Immunotherapy.Molecules (Basel, Switzerland) · 2022Review
- Review
- Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib.Cell biology international · 2021Article
- Co-treatment With Everolimus, an mTOR-Specific Antagonist, or Downregulation of ELK1 Enhances the Sensitivity of Pancreatic Cancer Cells to Genistein.Frontiers in cell and developmental biology · 2021Article
- The prediction of survival in Gastric Cancer based on a Robust 13-Gene Signature.Journal of Cancer · 2021Article
- A Novel Proteomic Method Reveals NLS Tagging of T-DM1 Contravenes Classical Nuclear Transport in a Model of HER2-Positive Breast Cancer.Molecular therapy. Methods & clinical development · 2020Article
- SFPQ and Tau: critical factors contributing to rapid progression of Alzheimer's disease.Acta neuropathologica · 2020Article
- Monitoring protein communities and their responses to therapeutics.Nature reviews. Drug discovery · 2020Review
- Global metabolomic profiling of trastuzumab resistant gastric cancer cells reveals major metabolic pathways and metabolic signatures based on UHPLC-Q exactive-MS/MS.RSC advances · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trastuzumab is an antibody-based therapy drug targeting HER2-overexpressing tumors. While it has been proven to be very successful initially, most patients eventually develop resistance to trastuzumab. The mechanism of drug resistance is not well understood. Identifying pathways that mediate trastuzumab resistance will improve our understanding of the underlying mechanism and is crucial for the development of therapeutic strategies to overcome resistance.Here we report a quantitative proteomics profiling of a trastuzumab-sensitive (T-S) gastric cancer cell line NCI N87 and a trastuzumab-resistant NCI N87 (T-R) subline generated by low-dose, continuous trastuzumab treatment. By identifying proteins differentially expressed in these two cell lines, we show that multiple pathways including mTOR, Wnt, DNA damage response and metabolic pathways are significantly altered. We further confirm by western blotting that protein levels of multiple components of the mTOR pathway, including mTOR, AKT and RPS6KB1, are increased, whereas AKT1S1 is decreased, suggesting the activation of mTOR pathway. Importantly, treatment of AZD8055, an mTOR inhibitor, leads to the decreased phosphorylation levels of mTOR downstream molecules RPS6KB1 at Thr421/Ser424 and AKT at Ser473. Furthermore, AZD8055 also preferentially reduces viability, and inhibits migration and invasion abilities of the T-R cells. Together, our findings indicate that mTOR pathway is among multiple signaling pathways that mediate trastuzumab resistance in NCI N87 T-R cells, and that mTOR inhibitors may be used to treat trastuzumab resistant, HER2-positive gastric cancer tumors.
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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.