ArticleBritish journal of cancer2020
YES1 amplification confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive cancer.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Exploiting YES1-Driven EGFR Expression Improves the Efficacy of EGFR Inhibitors.Molecular cancer research : MCR · 2025Article
- Navigating the Landscape of Resistance Mechanisms in Antibody-Drug Conjugates for Cancer Treatment.Targeted oncology · 2025Review
- Molecular Pharmacology of Dasatinib Provides Unique Insights into the Mechanistic Basis of Success and Failure of Targeted Cancer Therapy.ACS pharmacology & translational science · 2025Review
- Mechanisms of resistance to antibody-drug conjugates in cancer therapy: molecular basis and therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Exploring the role of YES1 kinase in regulating cisplatin resistance through iTRAQ-based quantitative proteomic analysis in urothelial carcinoma.American journal of cancer research · 2025Article
- Real-World Analysis of the Efficacy and Adverse Events of T-DM1 in Chinese Patients With HER2-Positive Breast Cancer.Breast cancer (Dove Medical Press) · 2025Article
- Neratinib plus dasatinib is highly synergistic in HER2-positive breast cancer in vitro and in vivo.Translational oncology · 2024Article
- Emerging Roles of YES1 in Cancer: The Putative Target in Drug Resistance.International journal of molecular sciences · 2024Review
- A renaissance for YES in cancer.Oncogene · 2023Review
- Role of YES1 signaling in tumor therapy resistance.Cancer innovation · 2023Review
- Targeting the Src N-terminal regulatory element in cancer.Oncotarget · 2023Article
- Resistance to antibody-drug conjugates in breast cancer: mechanisms and solutions.Cancer communications (London, England) · 2023Review
- Destabilized 3'UTR elements therapeutically degrade ERBB2 mRNA in drug-resistant ERBB2+ cancer models.Frontiers in genetics · 2023Article
- Heterogeneous delivery across the blood-brain barrier limits the efficacy of an EGFR-targeting antibody drug conjugate in glioblastoma.Neuro-oncology · 2021Article
- YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development.International journal of molecular sciences · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTrastuzumab-emtansine (T-DM1), one of the most potent HER2-targeted drugs, shows impressive efficacy in patients with HER2-positive breast cancers. However, resistance inevitably occurs and becomes a critical clinical problem.
methodsWe modelled the development of acquired resistance by exposing HER2-positive cells to escalating concentrations of T-DM1. Signalling pathways activation was detected by western blotting, gene expression was analysed by qRT-PCR and gene copy numbers were determined by qPCR. The role of Yes on resistance was confirmed by siRNA-mediated knockdown and stable transfection-mediated overexpression. The in vivo effects were tested in xenograft model.
resultsWe found that Yes is overexpressed in T-DM1-resistant cells owing to amplification of chromosome region 18p11.32, where the YES1 gene resides. Yes activated multiple proliferation-related signalling pathways, including EGFR, PI3K and MAPK, and led to cross-resistance to all types of HER2-targeted drugs, including antibody-drug conjugate, antibody and small molecule inhibitor. The outcome of this cross-resistance may be a clinically incurable condition. Importantly, we found that inhibiting Yes with dasatinib sensitised resistant cells in vitro and in vivo.
conclusionsOur study revealed that YES1 amplification conferred resistance to HER2-targeted drugs and suggested the potential application of the strategy of combining HER2 and Yes inhibition in the clinic.
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