ArticleMolecular cancer research : MCR2014
NF-κB activation-induced anti-apoptosis renders HER2-positive cells drug resistant and accelerates tumor growth.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Identification of novel therapeutic target genes in acquired lapatinib-resistant breast cancer by integrative meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Pooled it
- A study on the mechanism of action of B7H4 in HER2-positive gastric cancer and its sensitivity to trastuzumab therapy.Translational cancer research · 2026Article
- mRNA-laden LNP-enabled in situ CAR-macrophage alleviates liver fibrosis via inhibiting activated HSCs and modulating the immune microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Increased keratin 80 expression predicts poor prognosis and promotes oxaliplatin resistance in gastric cancer.World journal of gastroenterology · 2025Article
- FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies.Frontiers in pharmacology · 2023Review
- Pathophysiological role of ion channels and transporters in HER2-positive breast cancer.Cancer gene therapy · 2022Review
- Transglutaminase-2 mediates acquisition of neratinib resistance in metastatic breast cancer.Molecular biomedicine · 2022Article
- ERα36-GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells.International journal of molecular sciences · 2021Article
- RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer.Breast cancer research : BCR · 2021Article
- Article
- The Target Differences of Anti-Tumorigenesis Potential of Curcumin and its Analogues Against HER-2 Positive and Triple-Negative Breast Cancer Cells.Advanced pharmaceutical bulletin · 2021Article
- The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL.International journal of molecular sciences · 2020Review
- Intravenous leiomyomatosis is inclined to a solid entity different from uterine leiomyoma based on RNA-seq analysis with RT-qPCR validation.Cancer medicine · 2020Article
- Tumor Necrosis Factor α Blockade: An Opportunity to Tackle Breast Cancer.Frontiers in oncology · 2020Review
- Annotation and cluster analysis of long noncoding RNA linked to male sex and estrogen in cancers.NPJ precision oncology · 2020Article
- Combining RANK/RANKL and ERBB-2 targeting as a novel strategy in ERBB-2-positive breast carcinomas.Breast cancer research : BCR · 2019Article
- RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives.Journal of experimental & clinical cancer research : CR · 2019Review
- HER2, NF-Disease markers · 2019Article
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledBreast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are initially effective against HER2-positive breast cancer, but resistance inevitably occurs. We previously found that NF-κB is hyperactivated in a subset of HER2-positive breast cancer cells and tissue specimens. In this study, we report that constitutively active NF-κB rendered HER2-positive cancer cells resistant to anti-HER2 drugs and cells selected for lapatinib resistance upregulated NF-κB. In both circumstances, cells were antiapoptotic and grew rapidly as xenografts. Lapatinib-resistant cells were refractory to HER2 and NF-κB inhibitors alone but were sensitive to their combination, suggesting a novel therapeutic strategy. A subset of NF-κB-responsive genes was overexpressed in HER2-positive and triple-negative breast cancers, and patients with this NF-κB signature had poor clinical outcome. Anti-HER2 drug resistance may be a consequence of NF-κB activation, and selection for resistance results in NF-κB activation, suggesting that this transcription factor is central to oncogenesis and drug resistance. Clinically, the combined targeting of HER2 and NF-κB suggests a potential treatment paradigm for patients who relapse after anti-HER2 therapy. Patients with these cancers may be treated by simultaneously suppressing HER2 signaling and NF-κB activation. IMPLICATIONS: The combination of an inhibitor of IκB kinase (IKK) inhibitor and anti-HER2 drugs may be a novel treatment strategy for drug-resistant human breast cancers.
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