ArticleOncogene2004
Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 79 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.
A Phase III Double Blind Randomized Placebo Controlled Study of Trastuzumab as Short Duration Preoperative Therapy in Patients With HER2-neu Positive Operable Breast Cancer
A Randomized Trial With Factorial Design Comparing Fulvestrant ± Lapatinib ± Aromatase Inhibitor in Metastatic Breast Cancer Progressing After Aromatase Inhibitor Therapy
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 253 citations in OpenAlex.
- Lapatinib for treatment of advanced or metastasized breast cancer: systematic review.Sao Paulo medical journal = Revista paulista de medicina · 2009Pooled it
- Phase II study evaluating lapatinib in combination with nab-paclitaxel in HER2-overexpressing metastatic breast cancer patients who have received no more than one prior chemotherapeutic regimen.Breast cancer research and treatment · 2013Trial
- Trial
- Phase I pharmacokinetic studies evaluating single and multiple doses of oral GW572016, a dual EGFR-ErbB2 inhibitor, in healthy subjects.Investigational new drugs · 2005Trial
- Hotspot mutations in HER2 interfaces destabilize structure, causing breast cancer treatment failure.Oncogene · 2026Article
- Signaling pathways and potential therapeutic agents in trastuzumab-induced cardiotoxicity.Apoptosis : an international journal on programmed cell death · 2026Review
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- Review
- Automation of Drug Discovery through Cutting-edgeCurrent computer-aided drug design · 2024Review
- Development of a High-Affinity Antibody against the Tumor-Specific and Hyperactive 611-p95HER2 Isoform.Cancers · 2022Article
- Clinical implication of genetic composition and molecular mechanism on treatment strategies of HER2-positive breast cancers.Frontiers in oncology · 2022Review
- Rational Design of Novel Inhibitors of α-Glucosidase: An Application of Quantitative Structure Activity Relationship and Structure-Based Virtual Screening.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Selective ERBB2 and BCL2 Inhibition Is Synergistic for Mitochondrial-Mediated Apoptosis in MDS and AML Cells.Molecular cancer research : MCR · 2021Article
- Review
- Biomarkers in Her2- Positive Disease.Breast care (Basel, Switzerland) · 2020Review
- Lipid metabolic reprogramming as an emerging mechanism of resistance to kinase inhibitors in breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2020Article
- Targeting HER2 by Combination Therapies.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Article
- Article
- MicroRNA-133a Inhibits Proliferation of Gastric Cancer Cells by Downregulating ERBB2 Expression.Oncology research · 2017Article
- Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of the NH2 terminally truncated ErbB2 receptor (p95ErbB2) in breast cancer correlates with metastatic disease progression compared with the expression of full-length p185ErbB2. We now show that heregulin (HRG), but not EGF, stimulates p95ErbB2 phosphorylation in BT474 breast cancer cells. Furthermore, phospho-p95ErbB2 forms heterodimers with ErbB3, but not EGFR, while p185ErbB2 heterodimerizes with both EGFR and ErbB3. The predilection of p95ErbB2 to heterodimerize with ErbB3 provides an explanation for its regulation by HRG, an ErbB3 ligand. GW572016, a reversible small molecule inhibitor of EGFR and ErbB2 tyrosine kinases, inhibits baseline p95ErbB2 phosphorylation in BT474 cells and tumor xenografts. Inhibition of p95ErbB2, p185ErbB2, and EGFR phosphorylation by GW572016 resulted in the inhibition of downstream phospho-Erk1/2, phospho-AKT, and cyclin D steady-state protein levels. Increased phosphorylation of p95ErbB2 and AKT in response to HRG was abrogated to varying degrees by GW572016. In contrast, trastuzumab did not inhibit p95ErbB2 phosphorylation or the expression of downstream phospho-Erk1/2, phospho-AKT, or cyclin D. It is tempting to speculate that trastuzumab resistance may be mediated in part by the selection of p95ErbB2-expressing breast cancer cells capable of exerting potent growth and prosurvival signals through p95ErbB2-ErbB3 heterodimers. Thus, p95ErbB2 represents a target for therapeutic intervention, and one that is sensitive to GW572016 therapy.
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Identifiers
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.