ArticleCancer research2012
HER2 overexpression renders human breast cancers sensitive to PARP inhibition independently of any defect in homologous recombination DNA repair.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 75 citations in OpenAlex.
- Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells.Nucleic acids research · 2025Article
- Poly(ADP-ribose) polymerase-1 in breast cancers: expression level and its association in various molecular subtypes with a focus in Africa.Discover oncology · 2025Review
- Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer.Future medicinal chemistry · 2025Article
- A novel approach for breast cancer treatment: the multifaceted antitumor effects of rMeV-Hu191.Hereditas · 2024Article
- PARP Inhibitors in Breast Cancer: a Short Communication.Current oncology reports · 2024Review
- Standard-of-Care Treatment for HER2+ Metastatic Breast Cancer and Emerging Therapeutic Options.Breast cancer : basic and clinical research · 2024Review
- Combination Therapy with Trastuzumab and Niraparib: Quantifying Early Proliferative Alterations in HER2+ Breast Cancer Models.Biomedicines · 2023Article
- The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo.Gynecologic oncology · 2023Article
- PARP Inhibitor Inhibits the Vasculogenic Mimicry through a NF-κB-PTX3 Axis Signaling in Breast Cancer Cells.International journal of molecular sciences · 2022Article
- NetCellMatch: Multiscale Network-Based Matching of Cancer Cell Lines to Patients Using Graphical Wavelets.Chemistry & biodiversity · 2022Article
- Ginsenoside Rh1 Induces MCF-7 Cell Apoptosis and Autophagic Cell Death through ROS-Mediated Akt Signaling.Cancers · 2021Article
- Novel Aptamers Selected on Living Cells for Specific Recognition of Triple-Negative Breast Cancer.iScience · 2020Article
- PARP and PARG inhibitors in cancer treatment.Genes & development · 2020Review
- Trastuzumab-Resistant HER2Molecular cancer therapeutics · 2018Article
- PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs.International journal of molecular sciences · 2017Review
- Let-7 Status Is Crucial for PARP1 Expression in HER2-Overexpressing Breast Tumors.Molecular cancer research : MCR · 2017Article
- The Poly (ADP-Ribose) Polymerase Inhibitor Veliparib and Radiation Cause Significant Cell Line Dependent Metabolic Changes in Breast Cancer Cells.Scientific reports · 2016Article
- PARP1 enhances lung adenocarcinoma metastasis by novel mechanisms independent of DNA repair.Oncogene · 2016Article
- Nuclear PARP1 expression and its prognostic significance in breast cancer patients.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations.PloS one · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
HER2 overexpression in breast cancer confers increased tumor aggressiveness. Although anti-HER2 therapies have improved patient outcome, resistance ultimately occurs. PARP inhibitors target homologous recombination (HR)-deficient tumors, such as the BRCA-associated breast and ovarian cancers. In this study, we show that HER2+ breast cancers are susceptible to PARP inhibition independent of an HR deficiency. HER2 overexpression in HER2 negative breast cancer cells was sufficient to render cells susceptible to the PARP inhibitors ABT-888 and AZD-2281 both in vitro and in vivo, which was abrogated by HER2 reduction. In addition, ABT-888 significantly inhibited NF-κB (p65/RelA) transcriptional activity in HER2+ but not HER2 negative breast cancer cells. This corresponded with a reduction in phosphorylated p65 and total IKKα levels, with a concomitant increase in IκBα. Overexpression of p65 abrogated cellular sensitivity to ABT-888, whereas IκBα overexpression reduced cell viability to a similar extent as ABT-888. Therefore, susceptibility of HER2+ breast cancer cells to PARP inhibition may be because of inhibition of NF-κB signaling driven by HER2. Our findings indicate that PARP inhibitors may be a novel therapeutic strategy for sporadic HER2+ breast cancer patients.
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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.