ArticleMolecular cancer therapeutics2014
Nuclear epidermal growth factor receptor is a functional molecular target in triple-negative breast cancer.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
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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.
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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.
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Who cites it
39 citing papers in PubMed, 55 citations in OpenAlex.
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- MerTK Drives Proliferation and Metastatic Potential in Triple-Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Machine learning-guided differential gene expression analysis identifies a highly-connected seven-gene cluster in triple-negative breast cancer.BioMedicine · 2024Article
- Nuclear translocation of Axl contributes to the malignancy of oral cancer cells.Journal of dental sciences · 2024Article
- Advances in PET/CT Imaging for Breast Cancer.Journal of clinical medicine · 2023Review
- Nuclear export signal mutation of epidermal growth factor receptor enhances malignant phenotypes of cancer cells.American journal of cancer research · 2023Article
- Molecular Research and Treatment of Breast Cancer.International journal of molecular sciences · 2022Article
- RNA-binding protein p54Cell death & disease · 2022Article
- Primaquine Inhibits the Endosomal Trafficking and Nuclear Localization of EGFR and Induces the Apoptosis of Breast Cancer Cells by Nuclear EGFR/Stat3-Mediated c-Myc Downregulation.International journal of molecular sciences · 2021Article
- Article
- Review
- Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Epidermal Growth Factor-gold Nanoparticle Conjugates-induced Cellular Responses: Effect of Interfacial Parameters between Cell and Nanoparticle.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2021Article
- Canonical ErbB-2 isoform and ErbB-2 variant c located in the nucleus drive triple negative breast cancer growth.Oncogene · 2020Article
- Cetuximab PET delineated changes in cellular distribution of EGFR upon dasatinib treatment in triple negative breast cancer.Breast cancer research : BCR · 2020Article
- Valproic Acid Synergizes With Cisplatin and CetuximabFrontiers in cell and developmental biology · 2020Article
- A kinase inhibitor screen identifies a dual cdc7/CDK9 inhibitor to sensitise triple-negative breast cancer to EGFR-targeted therapy.Breast cancer research : BCR · 2019Article
Corrections and comments
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- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) is a subclass of breast cancers (i.e., estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) that have poor prognosis and very few identified molecular targets. Strikingly, a high percentage of TNBCs overexpresses the EGF receptor (EGFR), yet EGFR inhibition has yielded little clinical benefit. Over the last decade, advances in EGFR biology have established that EGFR functions in two distinct signaling pathways: (i) classical membrane-bound signaling and (ii) nuclear signaling. Previous studies have demonstrated that nuclear EGFR (nEGFR) can enhance resistance to anti-EGFR therapies and is correlated with poor overall survival in breast cancer. On the basis of these findings, we hypothesized that nEGFR may promote intrinsic resistance to cetuximab in TNBC. To examine this question, a battery of TNBC cell lines and human tumors were screened and found to express nEGFR. Knockdown of EGFR expression demonstrated that TNBC cell lines retained dependency on EGFR for proliferation, yet all cell lines were resistant to cetuximab. Furthermore, Src Family Kinases (SFKs) influenced nEGFR translocation in TNBC cell lines and in vivo tumor models, where inhibition of SFK activity led to potent reductions in nEGFR expression. Inhibition of nEGFR translocation led to a subsequent accumulation of EGFR on the plasma membrane, which greatly enhanced sensitivity of TNBC cells to cetuximab. Collectively, these data suggest that targeting both the nEGFR signaling pathway, through the inhibition of its nuclear transport, and the classical EGFR signaling pathway with cetuximab may be a viable approach for the treatment of patients with TNBC.
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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.