ArticleOncogene2022
Distinct roles of treatment schemes and BRCA2 on the restoration of homologous recombination DNA repair and PARP inhibitor resistance in ovarian cancer.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- Multiomics profiling and experiments in preclinical models revealed RAD51-IN-1 as a synergistic potentiator of anlotinib sensitivity.Science advances · 2026Trial
- Durvalumab and cediranib with and without olaparib in recurrent ovarian cancer: a phase II proof-of-concept study.Nature communications · 2026Trial
- Trial
- DHX9 Inhibition Enhances Paclitaxel Sensitivity by Inducing Mitotic Failure in Ovarian and Endometrial Cancers.Molecular cancer therapeutics · 2026Article
- JPI-547, a novel dual inhibitor of PARP1/2 and tankyrase is more effective than first-generation PARP inhibitors in preclinical BRCA1/2-mutated cancer models.British journal of cancer · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Ovarian Cancer Susceptibility and Chemosensitivity to KRAS Modulation.International journal of molecular sciences · 2026Article
- Eprenetapopt in combination with carboplatin in high-grade ovarian and triple negative breast cancer cell lines with acquired resistance to olaparib.Frontiers in oncology · 2026Article
- Hyperthermia-induced BRCA2 reduction potentiates PARPi sensitivity in BRCA2-proficient ovarian carcinoma.Discover oncology · 2025Article
- Article
- Phase II proof-of-concept study of durvalumab and cediranib with and without olaparib in recurrent ovarian cancer.Research square · 2025Article
- Genome-wide CRISPR activation screen identifies ARL11 as a sensitivity determinant of PARP inhibitor therapy.Cancer gene therapy · 2025Article
- Distinct effects of sacituzumab govitecan and berzosertib on DNA damage response in ovarian cancer.iScience · 2024Article
- AKT1 interacts with DHX9 to Mitigate R Loop-Induced Replication Stress in Ovarian Cancer.Cancer research · 2024Article
- Establishment and Molecular Characterization of an In Vitro Model for PARPi-Resistant Ovarian Cancer.Cancers · 2023Article
- PARP inhibitors, use early in the first-line maintenance therapy setting but with caution.Annals of translational medicine · 2023Article
- PARP Inhibitors and Proteins Interacting with SLX4.Cancers · 2023Review
- High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma.Pharmacogenomics and personalized medicine · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a major advance in ovarian cancer, now as a treatment and as a maintenance therapy in the upfront and recurrent settings. However, patients often develop resistance to PARPis, underlining the importance of dissecting resistance mechanisms. Here, we report different dosing/timing schemes of PARPi treatment in BRCA2-mutant PEO1 cells, resulting in the simultaneous development of distinct resistance mechanisms. PARPi-resistant variants PEO1/OlaJR, established by higher initial doses and short-term PARPi treatment, develops PARPi resistance by rapidly restoring functional BRCA2 and promoting drug efflux activity. In contrast, PEO1/OlaR, developed by lower initial doses with long-term PARPi exposure, shows no regained BRCA2 function but a mesenchymal-like phenotype with greater invasion ability, and exhibits activated ATR/CHK1 and suppressed EZH2/MUS81 signaling cascades to regain HR repair and fork stabilization, respectively. Our study suggests that PARPi resistance mechanisms can be governed by treatment strategies and have a molecular basis on BRCA2 functionality. Further, we define different mechanisms that may serve as useful biomarkers to assess subsequent treatment strategies in PARPi-resistant ovarian cancer.
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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.