ArticleCancer science2020
Acquired resistance to trastuzumab/pertuzumab or to T-DM1 in vivo can be overcome by HER2 kinase inhibition with TAS0728.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Real-world outcomes and safety of inetetamab plus pyrotinib and chemotherapy in HER2-positive metastatic breast cancer: A multicenter retrospective study.Therapeutic advances in medical oncology · 2026Article
- Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study.Signal transduction and targeted therapy · 2025Article
- Steroid hormone receptors, exome sequencing and treatment responsiveness of breast cancer patient-derived xenografts originated in a South American country.Scientific reports · 2025Article
- Antibody-drug conjugate: a newly developed biological missile for tumor treatment.Frontiers in oncology · 2025Review
- Mechanisms of resistance to antibody-drug conjugates in cancer therapy: molecular basis and therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Establishment of a trastuzumab-resistant extramammary Paget disease model: loss of PTEN as a potential mechanism.British journal of cancer · 2024Article
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- A prospective study of HER3 expression pre and post neoadjuvant therapy of different breast cancer subtypes: implications for HER3 imaging therapy guidance.Breast cancer research : BCR · 2024Article
- [Research Progress of Antibody-conjugated Drugs in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- Targeting Interleukin-13 Receptor α2 and EphA2 in Aggressive Breast Cancer Subtypes with Special References to Chimeric Antigen Receptor T-Cell Therapy.International journal of molecular sciences · 2024Review
- Generation and Characterization of Trastuzumab/Pertuzumab-Resistant HER2-Positive Breast Cancer Cell Lines.International journal of molecular sciences · 2023Article
- Manufacture and evaluation of a HER2-positive breast cancer immunotoxin 4D5Fv-PE25.Microbial cell factories · 2023Article
- Dual-targeting therapy against HER3/MET in human colorectal cancers.Cancer medicine · 2023Article
- Review
- Caveolin-1 temporal modulation enhances antibody drug efficacy in heterogeneous gastric cancer.Nature communications · 2022Article
- Antibody drug conjugate: the "biological missile" for targeted cancer therapy.Signal transduction and targeted therapy · 2022Review
- MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy.Cancer cell international · 2022Review
- Review
- New Insight to Overcome Tumor Resistance: An Overview from Cellular to Clinical Therapies.Life (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
HER2-targeting antibodies (trastuzumab, pertuzumab) and a HER2-directed antibody-drug conjugate (trastuzumab emtansine: T-DM1) are used for the treatment of HER2-overexpressing breast cancer. However, these treatments eventually become ineffective due to acquired resistance and there is an urgent need for alternative therapies. TAS0728 is a small-molecule, irreversible selective HER2 kinase inhibitor. In the present study, we established new in vivo models of cancer resistance by continuous exposure to a combination of trastuzumab and pertuzumab or to T-DM1 for evaluating the effect of TAS0728 on HER2 antibody-resistant populations. Treatment with trastuzumab and pertuzumab or with T-DM1 initially induced tumor regression in NCI-N87 xenografts. However, tumor regrowth during treatment indicated loss of drug effectiveness. In tumors with acquired resistance to trastuzumab and pertuzumab or to T-DM1, HER2-HER3 phosphorylation was retained. Switching to TAS0728 resulted in a significant anti-tumor effect associated with HER2-HER3 signal inhibition. No alternative receptor tyrosine kinase activation was observed in these resistant tumors. Furthermore, in a patient-derived xenograft model derived from breast cancer refractory to both trastuzumab/pertuzumab and T-DM1, TAS0728 exerted a potent anti-tumor effect. These results suggest that tumors with acquired resistance to trastuzumab and pertuzumab and to T-DM1 are still dependent on oncogenic HER2-HER3 signaling and are vulnerable to HER2 signal inhibition by TAS0728. These results provide a rationale for TAS0728 therapy for breast cancers that are refractory to established anti-HER2 therapies.
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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.