ArticleMolecular carcinogenesis2019
Activation of Wnt signaling promotes olaparib resistant ovarian cancer.
Article in Molecular carcinogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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The trial behind it
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Who cites it
69 citing papers in PubMed, 99 citations in OpenAlex.
- Trial
- AZD6738 overcomes acquired olaparib resistance in BRCA1 mutation triple-negative breast cancer through down-regulation of BRCA2 and RAD51.Scientific reports · 2026Article
- Ex Vivo Immuno-Oncology Platform Reveals Spatial T-cell Infiltration Patterns Linked to ATR Inhibition Responses in High-Grade Serous Ovarian Cancer.Cancer immunology research · 2026Article
- Metformin-A Type 2 Diabetes Mellitus Drug-And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Shaping the future one slice at a time: How 3D organotypic tumour slice models are driving drug discovery in ovarian cancer.Translational oncology · 2026Review
- SM08502-Mediated β-Catenin Repression Synergizes with Olaparib to Inhibit Tumor Progression.Cancer research communications · 2025Article
- Claudin-4 as a dual regulator of genome stability and immune evasion in high grade serous ovarian cancer.Scientific reports · 2025Article
- Identification of novel gene expression patterns and pathways involved in PARP-1 inhibitor resistance.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Evolutionary conservation and cancer implications of the WNT signaling pathway.Medical oncology (Northwood, London, England) · 2025Review
- Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.Journal of ovarian research · 2025Review
- Extensive epigenomic dysregulation is a hallmark of homologous recombination deficiency in triple-negative breast cancer.International journal of cancer · 2025Article
- Review
- PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy.Frontiers in immunology · 2025Review
- Distinct effects of sacituzumab govitecan and berzosertib on DNA damage response in ovarian cancer.iScience · 2024Article
- EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell-Dependent Manner.Molecular cancer research : MCR · 2024Article
- Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.Molecular cancer therapeutics · 2024Article
- Blocking the WNT/β-catenin pathway in cancer treatment:pharmacological targets and drug therapeutic potential.Heliyon · 2024Review
- BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer.Cancer research communications · 2024Article
- Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei.Cancer research communications · 2024Article
- VDX-111, a novel small molecule, induces necroptosis to inhibit ovarian cancer progression.Molecular carcinogenesis · 2024Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Epithelial ovarian cancer (EOC) has one of the highest death to incidence ratios among all cancers. High grade serous ovarian carcinoma (HGSOC) is the most common and deadliest EOC histotype due to the lack of therapeutic options following debulking surgery and platinum/taxane-based chemotherapies. For recurrent chemosensitive HGSOC, poly(ADP)-ribose polymerase inhibitors (PARPi; olaparib, rucaparib, or niraparib) represent an emerging treatment strategy. While PARPi are most effective in homologous recombination DNA repair-deficient (HRD) HGSOCs, recent studies have observed a significant benefit in non-HRD HGSOCs. However, all HGSOC patients are likely to acquire resistance. Therefore, there is an urgent clinical need to understand PARPi resistance and to introduce novel combinatorial therapies to manage PARPi resistance and extend HGSOC disease-free intervals. In a panel of HGSOC cell lines, we established matched olaparib sensitive and resistant cells. Transcriptome analysis of the matched olaparib-sensitive vs -resistant cells revealed activation of the Wnt signaling pathway and consequently increased TCF transcriptional activity in PARPi-resistant cells. Forced activation of canonical Wnt signaling in several PARPi-sensitive cells via WNT3A reduced olaparib and rucaparib sensitivity. PARPi resistant cells were sensitive to inhibition of Wnt signaling using the FDA-approved compound, pyrvinium pamoate, which has been shown to promote downregulation of β-catenin. In both an HGSOC cell line and a patient-derived xenograft model, we observed that combining pyrvinium pamoate with olaparib resulted in a significant decrease in tumor burden. This study demonstrates that Wnt signaling can mediate PARPi resistance in HGSOC and provides a clinical rationale for combining PARP and Wnt inhibitors.
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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.