ArticleProceedings of the National Academy of Sciences of the United States of America2006
A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04034589 (Phase II Study of Pyrotinib in Combination With Fulvestrant in Patients With Human Epidermal Growth Factor Receptor 2), which is not on this map. Cited by 177 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.
Phase II Study of Pyrotinib in Combination With Fulvestrant in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive，Hormone Receptor（HR）-Positive Metastatic Breast Cancer
Who cites it
177 citing papers in PubMed, 377 citations in OpenAlex.
- Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109).Breast cancer research : BCR · 2024Trial
- Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor.PloS one · 2015Trial
- Pathologic complete response after preoperative anti-HER2 therapy correlates with alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling.BMC research notes · 2013Trial
- Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib.The oncologist · 2010Trial
- A phase I-II study of combined blockade of the ErbB receptor network with trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic breast cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2008Trial
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- Routine biomarkers map response probability in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2 blockade.BMC cancer · 2026Observational
- An Updated Narrative Review on the Therapeutic Potential of Resveratrol in the Treatment of Cancer.Health science reports · 2026Article
- Advances in Targeting HER2 across Cancer Subtypes: A Pan-Tumor Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Can neoadjuvant chemotherapy be replaced with immune checkpoint blockade combined with dual anti-HER2 antibodies for HER2-enriched breast cancer?Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Article
- Anti-HER2 plus endocrine therapy versus anti-HER2 plus chemotherapy in hormone receptor-positive and HER2-positive metastatic breast cancer: a retrospective study.International journal of clinical oncology · 2025Article
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Pre-Clinical Rationale for Amcenestrant Combinations in HER2+/ER+ Breast Cancer.International journal of molecular sciences · 2025Article
- Genomic profiling and comparative analysis of male versus female metastatic breast cancer across subtypes.Breast cancer research : BCR · 2024Article
- EB1089 Increases the Antiproliferative Response of Lapatinib in Combination with Antiestrogens in HER2-Positive Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives.Nature reviews. Clinical oncology · 2024Review
- The inhibitory effect of trastuzumab on BT474 triple‑positive breast cancer cell viability is reversed by the combination of progesterone and estradiol.Oncology letters · 2024Article
- Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients.Therapeutic advances in medical oncology · 2024Review
- Role of Fork-Head Box Genes in Breast Cancer: From Drug Resistance to Therapeutic Targets.Biomedicines · 2023Review
117 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
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of acquired resistance to ErbB2 tyrosine kinase inhibitors limits the clinical efficacy of this class of cancer therapeutics. Little is known about the mechanism(s) of acquired resistance to these agents. Here we establish a model of acquired resistance to N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2 (methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (lapatinib), an inhibitor of ErbB2 and ErbB1 tyrosine kinases by chronically exposing lapatinib-sensitive ErbB2-overexpressing breast cancer cells to lapatinib, simulating the clinic where lapatinib is administered on a daily chronic basis. Analysis of baseline gene expression in acquired lapatinib-resistant and parental cells indicates estrogen receptor (ER) signaling involvement in the development of resistance. Using gene interference, we confirm that acquired resistance to lapatinib is mediated by a switch in cell survival dependence and regulation of a key antiapoptotic mediator from ErbB2 alone to codependence upon ER and ErbB2 rather than loss of ErbB2 expression or insensitivity of ErbB2 signaling to lapatinib. Increased ER signaling in response to lapatinib is enhanced by the activation of factors facilitating the transcriptional activity of ER, notably FOXO3a and caveolin-1. Importantly, we confirm that lapatinib induces ER signaling in tumor biopsies from patients with ErbB2-overexpressing breast cancers receiving lapatinib therapy. These findings provided the rationale for preventing the development of acquired resistance by simultaneously inhibiting both ER and ErbB2 signaling pathways. Establishing clinically relevant models of acquired resistance to ErbB2 kinase inhibitors will enhance therapeutic strategies to improve clinical outcomes for patients with ErbB2-overexpressing breast cancers.
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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.