ArticlePloS one2011
Differential impact of EGFR-targeted therapies on hypoxia responses: implications for treatment sensitivity in triple-negative metastatic breast cancer.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Insights into the Emerging Therapeutic Targets of Triple-negative Breast Cancer.Current cancer drug targets · 2025Review
- The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.Cell communication and signaling : CCS · 2024Review
- Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer.Biomarker research · 2023Review
- Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies.Journal of enzyme inhibition and medicinal chemistry · 2022Review
- Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy.American journal of cancer research · 2021Review
- Tissue factor as a new target for CAR-NK cell immunotherapy of triple-negative breast cancer.Scientific reports · 2020Article
- Hypoxia-inducible factor-1 signaling pathway influences the sensitivity of HCC827 cells to gefitinib.Oncology letters · 2019Article
- Metastatic and triple-negative breast cancer: challenges and treatment options.Drug delivery and translational research · 2018Review
- Targeting Tissue Factor for Immunotherapy of Triple-Negative Breast Cancer Using a Second-Generation ICON.Cancer immunology research · 2018Article
- Quantification of hypoxia-related gene expression as a potential approach for clinical outcome prediction in breast cancer.PloS one · 2017Article
- Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors.Advanced healthcare materials · 2016Article
- Influence of allelic Variations of hypoxia-related and DNA repair genes on patient outcome and toxicity in head and neck cancer treated with radiotherapy plus cetuximab.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2016Article
- Article
- Cancer metastasis and EGFR signaling is suppressed by amiodarone-induced versican V2.Oncotarget · 2015Article
- Stimulus-dependent differences in signalling regulate epithelial-mesenchymal plasticity and change the effects of drugs in breast cancer cell lines.Cell communication and signaling : CCS · 2015Article
- Triple negative breast carcinoma EGFR amplification is not associated with EGFR, Kras or ALK mutations.British journal of cancer · 2014Article
- Run-in phase III trial design with pharmacodynamics predictive biomarkers.Journal of the National Cancer Institute · 2013Article
- BTG2 inhibits the proliferation, invasion, and apoptosis of MDA-MB-231 triple-negative breast cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- The potential role of nanotechnology in therapeutic approaches for triple negative breast cancer.Pharmaceutics · 2013Article
- The effects of RKIP gene expression on the biological characteristics of human triple-negative breast cancer cells in vitro.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn solid tumors, such as breast cancer, cells are exposed to hypoxia. Cancer cells adapt their metabolism by activating hypoxia-inducible factors (HIFs) that promote the transcription of genes involved in processes such as cell survival, drug resistance and metastasis. HIF-1 is also induced in an oxygen-independent manner through the activation of epidermal growth factor receptor tyrosine kinase (EGFR-TK). Triple-negative breast cancer (TNBC) is a subtype of invasive breast cancer characterized by negative expression of hormonal and HER2 receptors, and this subtype generally overexpresses EGFR. Sensitivity to three EGFR inhibitors (cetuximab, gefitinib and lapatinib, an HER2/EGFR-TK inhibitor) was evaluated in a metastatic TNBC cell model (MDA-MB-231), and the impact of these drugs on the activity and stability of HIF was assessed. METHODOLOGY/PRINCIPAL
findingsMDA-MB-231 cells were genetically modified to stably express an enhanced green fluorescent protein (EGFP) induced by hypoxia; the Ca9-GFP cell model reports HIF activity, whereas GFP-P564 reports HIF stability. The reporter signal was monitored by flow cytometry. HIF-1 DNA-binding activity, cell migration and viability were also evaluated in response to EGFR inhibitors. Cell fluorescence signals strongly increased under hypoxic conditions (> 30-fold). Cetuximab and lapatinib did not affect the signal induced by hypoxia, whereas gefitinib sharply reduced its intensity in both cell models and also diminished HIF-1 alpha levels and HIF-1 DNA-binding activity in MDA-MB-231 cells. This gefitinib feature was associated with its ability to inhibit MDA-MB-231 cell migration and to induce cell mortality in a dose-dependent manner. Cetuximab and lapatinib had no effect on cell migration or cell viability.
conclusionResistance to cetuximab and lapatinib and sensitivity to gefitinib were associated with their ability to modulate HIF activity and stability. In conclusion, downregulation of HIF-1 through EGFR signaling seems to be required for the induction of a positive response to EGFR-targeted therapies in TNBC.
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