ArticleEBioMedicine2020
BET, SRC, and BCL2 family inhibitors are synergistic drug combinations with PARP inhibitors in ovarian cancer.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting.International journal of molecular sciences · 2026Review
- PARP inhibitors induce a senescence phenotype in non-small cell lung carcinoma cell lines.FEBS open bio · 2026Article
- Olaparib synergy screen reveals Exemestane induces replication stress in triple-negative breast cancer.Molecular oncology · 2025Article
- Understanding the Functional Dependence and Inhibition of the Bcl‑2 Pro-Survival Proteins in a Wide Spectrum of Cancers toward Precision Medicine.ACS pharmacology & translational science · 2025Article
- Characterization of tumor prognosis and sensitive chemotherapy drugs based on cuproptosis-related gene signature in ovarian cancer.BMC women's health · 2025Article
- Antineoplastic Drug Synergy of Artesunate with Navitoclax in Models of High-Grade Serous Ovarian Cancer.Cancers · 2024Article
- Article
- First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma.Molecular cancer therapeutics · 2023Article
- Bcl-2 family inhibitors sensitize human cancer models to therapy.Cell death & disease · 2023Article
- Discovery of Ruthenium(II) Metallocompound and Olaparib Synergy for Cancer Combination Therapy.Journal of medicinal chemistry · 2023Article
- Using graph-based model to identify cell specific synthetic lethal effects.Computational and structural biotechnology journal · 2023Article
- Review
- pH-Responsive Hyaluronic Acid Nanoparticles for Enhanced Triple Negative Breast Cancer Therapy.International journal of nanomedicine · 2022Article
- The role of protein acetylation in carcinogenesis and targeted drug discovery.Frontiers in endocrinology · 2022Review
- TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing β-Catenin in colorectal cancer cells.American journal of cancer research · 2022Article
- Strategies in Overcoming Homologous Recombination Proficiency and PARP Inhibitor Resistance.Molecular cancer therapeutics · 2021Review
- Synergistic AHR Binding Pathway with EMT Effects on Serous Ovarian Tumors Recognized by Multidisciplinary Integrated Analysis.Biomedicines · 2021Article
- Targeting BET Proteins BRD2 and BRD3 in Combination with PI3K-AKT Inhibition as a Therapeutic Strategy for Ovarian Clear Cell Carcinoma.Molecular cancer therapeutics · 2021Article
- An expanded universe of cancer targets.Cell · 2021Review
- Histone Modifying Enzymes in Gynaecological Cancers.Cancers · 2021Review
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundHomologous recombination deficiencies (HRD) are present in approximately half of epithelial ovarian cancers, for which PARP inhibitors (PARPi) are becoming a preferred treatment option. However, a considerable proportion of these carcinomas acquire resistance or harbour de novo resistance, posing a significant challenge to treatment.
methodsTo identify new combinatorial therapeutics to overcome resistance to PARPi, we employed high-throughput conditional RNAi and drug screening of patient-derived ovarian cancer cells. To prioritise clinically relevant drug combinations, we integrated empirical validation with analysis of The Cancer Genome Atlas (TCGA) and Genomics of Drug Sensitivity in Cancer (GDSC) datasets to nominate candidate targets and drugs, reaching three main findings.
findingsFirstly, we found that the PARPi rucaparib enhanced the effect of BET inhibitors (CPI-203 & CPI-0610) irrespective of clinical subtype or HRD status. Additional drug combination screens identified that dasatinib, a non-receptor tyrosine kinase inhibitor, augmented the effects of rucaparib and BET inhibitors, proposing a potential broadly applicable triple-drug combination for high-grade serous and clear cell ovarian carcinomas. Secondly, rucaparib synergised with the BCL2 family inhibitor navitoclax, with preferential activity in ovarian carcinomas that harbour alterations in BRCA1/2, BARD1, or MSH2/6. Thirdly, we identified potentially antagonistic drug combinations between the PARPi rucaparib and vinca alkaloids, anthracyclines, and antimetabolites, cautioning their use in the clinic.
interpretationThese findings propose therapeutic strategies to address PARP inhibitor resistance using agents that are already approved or are in clinical development, with the potential for rapid translation to benefit a broad population of ovarian cancer patients.
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