ArticleProceedings of the National Academy of Sciences of the United States of America2012
Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers.
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Who cites it
190 citing papers in PubMed, 324 citations in OpenAlex.
- Auranofin Potentiates Cisplatin Response in the Setting of Context-Dependent NOTCH-Associated Signaling States in Endometrial Cancer.Cancer research communications · 2026Article
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Chemotherapy Enrichment of ID Family Expression Is Associated with IL-6 Signaling in Ovarian Cancer.Cancers · 2026Article
- A novel humanized immune stroma PDX cancer model for therapeutic studies.Cancer immunology, immunotherapy : CII · 2026Article
- Prolyl-isomerase Pin1 drives platinum resistance by regulating Notch3 stability and function in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- NOTCH1 intracellular domain stabilization by MDM2 plays a major role in NSCLC response to platinum.EMBO molecular medicine · 2026Article
- The role of pluripotency regulators in triple-negative breast cancer immune response.Frontiers in genetics · 2026Review
- Molecular impact of NOTCH signaling dysregulation on ovarian cancer progression, chemoresistance, and taxane response.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Auranofin Synergizes with Cisplatin in Reducing Tumor Burden of NOTCH-Dependent Ovarian Cancer.Cancer research communications · 2025Article
- Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.Journal of ovarian research · 2025Review
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- Identification of Sphingosine Kinase 1 as a Novel Protein Regulated by High Molecular Weight Hyaluronan in Ovarian Cancer.Journal of cellular and molecular medicine · 2025Article
- Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance.Journal of hematology & oncology · 2025Review
- DOT1L Mediates Stem Cell Maintenance and Represents a Therapeutic Vulnerability in Cancer.Cancer research · 2025Review
- Stemness-Relevant Gene Signature for Chemotherapeutic Response and Prognosis Prediction in Ovarian Cancer.Stem cells international · 2025Article
- The role of notch signaling pathway in cancer: mechanistic insights, therapeutic potential, and clinical progress.Frontiers in immunology · 2025Review
- Therapeutic innovations in triple negative breast cancer: integrating molecular targeting and monoclonal antibody strategies.Frontiers in oncology · 2025Review
- Beyond tumor‑associated macrophages involved in spheroid formation and dissemination: Novel insights for ovarian cancer therapy (Review).International journal of oncology · 2024Review
- Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.British journal of cancer · 2024Article
130 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). This study demonstrates that the Notch signaling pathway and Notch3 in particular are critical for the regulation of CSCs and tumor resistance to platinum. We show that Notch3 overexpression in tumor cells results in expansion of CSCs and increased platinum chemoresistance. In contrast, γ-secretase inhibitor (GSI), a Notch pathway inhibitor, depletes CSCs and increases tumor sensitivity to platinum. Similarly, a Notch3 siRNA knockdown increases the response to platinum therapy, further demonstrating that modulation of tumor chemosensitivity by GSI is Notch specific. Most importantly, the cisplatin/GSI combination is the only treatment that effectively eliminates both CSCs and the bulk of tumor cells, indicating that a dual combination targeting both populations is needed for tumor eradication. In addition, we found that the cisplatin/GSI combination therapy has a synergistic cytotoxic effect in Notch-dependent tumor cells by enhancing the DNA-damage response, G(2)/M cell-cycle arrest, and apoptosis. Based on these results, we conclude that targeting the Notch pathway could significantly increase tumor sensitivity to platinum therapy. Our study suggests important clinical applications for targeting Notch as part of novel treatment strategies upon diagnosis of ovarian cancer and at recurrence. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increasingly platinum resistant.
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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.