ReviewCancers2017
HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance.
Review in Cancers, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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
47 citing papers in PubMed, 74 citations in OpenAlex.
- Article
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- Inhibition of TFF3 synergizes with c-MET inhibitors to decrease the CSC-like phenotype and metastatic burden in ER+HER2+ mammary carcinoma.Cell death & disease · 2025Article
- HER2-positive gastric cancer: from targeted therapy to CAR-T cell therapy.Frontiers in immunology · 2025Review
- Multiparametric profiling of HER2-enriched extracellular vesicles in breast cancer using Single Extracellular VEsicle Nanoscopy.Journal of nanobiotechnology · 2024Article
- Concise review: breast cancer stems cells and their role in metastases.Annals of medicine and surgery (2012) · 2024Review
- Article
- Molecular imprinting of miR-559 on a peptide-immobilized poly L-DOPA/silica core-shell and in vitro investigating its effects on HER2-positive breast cancer cells.Drug delivery and translational research · 2023Article
- Advances of nanotechnology applied to cancer stem cells.World journal of stem cells · 2023Review
- Resistance to antibody-drug conjugates in breast cancer: mechanisms and solutions.Cancer communications (London, England) · 2023Review
- Resistance to Trastuzumab.Cancers · 2022Review
- Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems.Stem cell reviews and reports · 2022Review
- Galectin-3 enhances trastuzumab resistance by regulating cancer malignancy and stemness in HER2-positive breast cancer cells.Thoracic cancer · 2022Article
- Circulating Proteins Associated with Response and Resistance to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.Cancers · 2022Article
- Epithelial-to-Mesenchymal Transition Signaling Pathways Responsible for Breast Cancer Metastasis.Cellular and molecular bioengineering · 2022Review
- PKC-mediated phosphorylation and activation of the MEK/ERK pathway as a mechanism of acquired trastuzumab resistance in HER2-positive breast cancer.Frontiers in endocrinology · 2022Article
- Modulatory role of miRNAs in thyroid and breast cancer progression and insights into their therapeutic manipulation.Current research in pharmacology and drug discovery · 2022Review
- A Tetravalent Biparatopic Antibody Causes Strong HER2 Internalization and Inhibits Cellular Proliferation.Life (Basel, Switzerland) · 2021Article
- Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs). HER2 shedding results in the accumulation of intracellular carboxyl-terminal HER2 (p95HER2), which is a common phenomenon in trastuzumab-resistant tumors and is suggested as a predictive marker for trastuzumab resistance. Up-regulation of the metalloproteinases is a poor prognosis factor and is commonly seen in mesenchymal-like cancer stem cells that are risen during epithelial to mesenchymal transition (EMT) of tumor cells. HER2 cleavage during EMT can explain why secondary metastatic tumors with high percentage of mesenchymal-like cancer stem cells are mostly resistant to trastuzumab but still sensitive to lapatinib. Importantly, many studies report HER2 interaction with oncogenic/stemness signaling pathways including TGF-β/Smad, Wnt/β-catenin, Notch, JAK/STAT and Hedgehog. HER2 overexpression promotes EMT and the emergence of cancer stem cell properties in BC. Increased expression and activation of metalloproteinases during EMT leads to proteolytic cleavage and shedding of HER2 receptor, which downregulates HER2 extracellular domain and eventually increases trastuzumab resistance. Here, we review the hypothesis that a negative feedback loop between HER2 and stemness signaling drives resistance of BC to trastuzumab.
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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.