ArticleThoracic cancer2015
Activated estrogen receptor-mitogen-activated protein kinases cross talk confer acquired resistance to lapatinib.
Article in Thoracic cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
12 citing papers in PubMed, 15 citations in OpenAlex.
- Molecular Mechanisms Underlying Recurrence in Triple-Positive Breast Cancer (ER+/PR+/HER2+) and Potential Repurposing of Multi-Target Inhibitors.International journal of molecular sciences · 2026Review
- EB1089 Increases the Antiproliferative Response of Lapatinib in Combination with Antiestrogens in HER2-Positive Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Trastuzumab-resistant breast cancer cells-derived tumor xenograft models exhibit distinct sensitivity to lapatinib treatment in vivo.Biological procedures online · 2023Article
- Estrogen/HER2 receptor crosstalk in breast cancer: combination therapies to improve outcomes for patients with hormone receptor-positive/HER2-positive breast cancer.NPJ breast cancer · 2023Review
- Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway.International journal of medical sciences · 2023Article
- Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity.International journal of molecular sciences · 2020Review
- Gene signatures and potential therapeutic targets of amino acid metabolism in estrogen receptor-positive breast cancer.American journal of cancer research · 2020Article
- Review
- Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment.OncoTargets and therapy · 2019Review
- Caveolin-1: An Oxidative Stress-Related Target for Cancer Prevention.Oxidative medicine and cellular longevity · 2017Review
- Effect of Fu-Zheng-Xiao-Liu Granules on Expression of Human Epidermal Growth Factor Receptor 2 (HER-2) and Proliferation and Apoptosis of Breast Cancer Cell Line SKBR-3.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells.Open biology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe efficacy of lapatinib is limited by the development of acquired resistance. The aim of this study was to investigate the role of estrogen receptor (ER) signaling compensatory activation in acquired resistance to lapatinib in breast cancer cells BT474 and the related mechanism.
methodsAcquired resistant cell model resistant (r)BT474 was generated with an increasing concentration of lapatinib. Real-time polymerase chain reaction and Western blotting were used to determine the changes of human epidermal growth factor receptor (HER)2 and ER pathways in breast cancer cell BT474 after treatment with lapatinib and the distinction between BT474 and rBT474. Methyl thiazolyl tetrazolium and colony formation assays were employed to detect the proliferation of rBT474 and BT474 cells treated with lapatinib and/or an ER inhibitor, fulvestrant, respectively.
resultsLapatinib could inhibit phosphorylation of HER2 and induce expression of forkhead-box protein O3a and progesterone receptor. Acquired resistant cell model rBT474 could grow in the presence of 5 μM lapatinib, with an apoptosis rate of only 5%. Significant inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) pathway and the activation of the mitogen-activated protein kinases (MAPK) and ER pathways were detected in rBT474, compared with BT474. Furthermore, the expressions of Src phosphorylation and caveolin-1 were also upregulated. The viability of rBT474 was markedly suppressed by the lapatinib/fulvestrant combination in vitro, confirmed by the BT474 xenograft model.
conclusionER signaling compensatory activation may partly contribute to lapatinib acquired resistance in HER2-overexpressing/ERα-positive breast cancer cells, which might be related to PI3K/AKT inhibition and MAPK pathway activation.
Indexed as
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.