ArticleOncotarget2016
A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Nestin overexpression reduces the sensitivity of gastric cancer cells to trastuzumab.Journal of gastrointestinal oncology · 2023Article
- Role of NRF2 in Ovarian Cancer.Antioxidants (Basel, Switzerland) · 2022Review
- Comprehensive overview of Nrf2-related epigenetic regulations involved in ischemia-reperfusion injury.Theranostics · 2022Review
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- Targeting Nrf2 may reverse the drug resistance in ovarian cancer.Cancer cell international · 2021Review
- Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas.Frontiers in pharmacology · 2021Article
- NRF2-Related Epigenetic Modifications in Cardiac and Vascular Complications of Diabetes Mellitus.Frontiers in endocrinology · 2021Review
- Nuclear factor erythroid 2-related factor 2 modulates HER4 receptor in ovarian cancer cells to influence their sensitivity to tyrosine kinase inhibitors.Exploration of targeted anti-tumor therapy · 2021Article
- Reducing toxic reactive carbonyl species in e-cigarette emissions: testing a harm-reduction strategy based on dicarbonyl trapping.RSC advances · 2020Article
- Nrf2 Inhibitor, Brusatol in Combination with Trastuzumab Exerts Synergistic Antitumor Activity in HER2-Positive Cancers by Inhibiting Nrf2/HO-1 and HER2-AKT/ERK1/2 Pathways.Oxidative medicine and cellular longevity · 2020Article
- Targeting HER2 in patient-derived xenograft ovarian cancer models sensitizes tumors to chemotherapy.Molecular oncology · 2019Article
- Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Mechanisms Underlying the Action and Synergism of Trastuzumab and Pertuzumab in Targeting HER2-Positive Breast Cancer.Cancers · 2018Review
- Natural killer cells inhibit metastasis of ovarian carcinoma cells and show therapeutic effects in a murine model of ovarian cancer.Experimental and therapeutic medicine · 2018Article
- EGFR-Targeted Immunotoxin Exerts Antitumor Effects on Esophageal Cancers by Increasing ROS Accumulation and Inducing Apoptosis via Inhibition of the Nrf2-Keap1 Pathway.Journal of immunology research · 2018Article
- Strange Bedfellows: Nuclear Factor, Erythroid 2-Like 2 (Nrf2) and Hypoxia-Inducible Factor 1 (HIF-1) in Tumor Hypoxia.Antioxidants (Basel, Switzerland) · 2017Review
- NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib.Oxidative medicine and cellular longevity · 2017Article
- Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy.Oxidative medicine and cellular longevity · 2017Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2.HER2 targeting by antibodies inhibited growth in association with persistent generation of reactive oxygen species (ROS), glutathione (GSH) depletion, reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell lines. The combination of antibodies produced more potent effects than single antibody alone; downregulated NRF2 substrates by repressing the Antioxidant Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We showed the antibody combination produced increased methylation at the NRF2 promoter consistent with repression of NRF2 antioxidant function, as HDAC and methylation inhibitors reversed such produced transcriptional effects. These findings demonstrate a novel mechanism and role for NRF2 in mediating the response of cancer cells to the combination of Trastuzumab and Pertuzumab and reinforce the importance of NRF2 in drug resistance and as a key anticancer target.
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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.