ArticleScientific reports2015
Trastuzumab resistance induces EMT to transform HER2(+) PTEN(-) to a triple negative breast cancer that requires unique treatment options.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Pooled it
- Adjuvant therapies by anthocyanins potentially mitigating drug resistance and metastatic disease risks in stratified breast cancers: the 3PM-conceptual innovation targeted to NF-kappaB/EMT plasticity.The EPMA journal · 2026Article
- Effects of Eribulin on Epithelial-Mesenchymal Plasticity in Patient-Derived Breast Cancer Cultures and Excised Tissues.Cancers · 2026Article
- Review
- Antibody-Drug Conjugates in Breast Cancer: Therapeutic-Window Engineering, Tumor Heterogeneity, and Immunotherapy Combinations.Drug design, development and therapy · 2026Review
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Biomarkers, isolation methods, and therapeutic implications of breast cancer stem cells.Cancer pathogenesis and therapy · 2025Review
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- Hedgehog Pathway Is a Regulator of Stemness in HER2-Positive Trastuzumab-Resistant Breast Cancer.International journal of molecular sciences · 2024Article
- Targeting ITGβ3 to Overcome Trastuzumab Resistance through Epithelial-Mesenchymal Transition Regulation in HER2-Positive Breast Cancer.International journal of molecular sciences · 2024Article
- Comprehensive molecular interaction map of TGFβ induced epithelial to mesenchymal transition in breast cancer.NPJ systems biology and applications · 2024Article
- No Interference of H9 Extract on Trastuzumab Pharmacokinetics in Their Combinations.International journal of molecular sciences · 2023Article
- Interplay of broccoli/broccoli sprout bioactives with gut microbiota in reducing inflammation in inflammatory bowel diseases.The Journal of nutritional biochemistry · 2023Review
- Revisiting Epithelial Carcinogenesis.International journal of molecular sciences · 2022Article
- Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance.Frontiers in oncology · 2022Review
- Evolution of HER2-positive mammary carcinoma: HER2 loss reveals claudin-low traits in cancer progression.Oncogenesis · 2021Article
- Cancer Stem Cells-Key Players in Tumor Relapse.Cancers · 2021Review
- Carboxypeptidase A4 negatively correlates with p53 expression and regulates the stemness of breast cancer cells.International journal of medical sciences · 2021Article
- Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment.Journal of hematology & oncology · 2020Review
- Epithelial-Mesenchymal Transition Programs and Cancer Stem Cell Phenotypes: Mediators of Breast Cancer Therapy Resistance.Molecular cancer research : MCR · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Although trastuzumab is an effective treatment in early stage HER2(+) breast cancer the majority of advanced HER2(+) breast cancers develop trastuzumab resistance, especially in the 40% of breast cancers with loss of PTEN. However, HER2(+) breast cancer patients continue to receive trastuzumab regardless PTEN status and the consequence of therapy in these patients is unknown. We demonstrate that continued use of trastuzumab in HER2(+) cells with loss of PTEN induces the epithelial-mesenchymal transition (EMT) and transform HER2(+) to a triple negative breast cancer. These transformed cells exhibited mesenchymal morphology and gene expression markers, while parent HER2(+) cells showed epithelial morphology and markers. The transformed cells exhibited loss of dependence on ERBB family signaling (such as HER2, HER3, HER4, BTC, HRG, EGF) and reduced estrogen and progesterone receptors. Continued use of trastuzumab in HER2(+) PTEN(-) cells increased the frequency of cancer stem cells (CSCs) and metastasis potential. Strikingly, parental HER2(+) cells and transformed resistant cells respond to treatment differently. Transformed resistant cells were sensitive to chemical probe (sulforaphane) through inhibition of IL-6/STAT3/NF-κB positive feedback loop whereas parental HER2(+) cells did not respond. This data suggests that trastuzumab resistance in HER2(+) PTEN- breast cancer induces EMT and subtype switching, which requires unique treatment options.
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What OpenQuestion holds
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.