ArticleGynecologic oncology2021
Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.
Article in Gynecologic oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Acetylation in ovarian cancer: mechanistic insights into drug resistance and emerging therapeutic opportunities.Journal of ovarian research · 2026Review
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- Targeting RAD52 overcomes PARP inhibitor resistance in preclinicalbioRxiv : the preprint server for biology · 2025Article
- Homologous Recombination Proficiency in High-Grade Serous Epithelial Ovarian Cancer Tumors: The Dark Side of the Moon.Current issues in molecular biology · 2025Review
- A novel deacetylase inhibitor KLX suppresses liver fibrosis by deacetylating PPARγ through promoting ubiquitination-mediated HDAC1 degradation.Science China. Life sciences · 2025Article
- New and Effective Inhibitor of Class I HDACs, Eimbinostat, Reduces the Growth of Hematologic Cancer Cells and Triggers Apoptosis.Pharmaceutics · 2025Article
- Combination strategies with PARP inhibitors in BRCA-mutated triple-negative breast cancer: overcoming resistance mechanisms.Oncogene · 2025Review
- The power and the promise of epigenetic drugs in oncology.Frontiers in genetics · 2025Review
- Niraparib plays synergistic antitumor effects with NRT in a mouse ovarian cancer model with HRP.Translational oncology · 2024Article
- Combination drug screen identifies synergistic drug interaction of BCL-XL and class I histone deacetylase inhibitors in MYC-amplified medulloblastoma cells.Journal of neuro-oncology · 2024Article
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Homologous recombination proficient subtypes of high-grade serous ovarian cancer: treatment options for a poor prognosis group.Frontiers in oncology · 2024Review
- Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells.Journal of neuro-oncology · 2023Article
- FAK inhibitor PF-562271 inhibits the migration and proliferation of high-grade serous ovarian cancer cells through FAK and FAK mediated cell cycle arrest.Medical oncology (Northwood, London, England) · 2023Article
- Article
- Differential histone deacetylase inhibitor-induced perturbations of the global proteome landscape in the setting of high-grade serous ovarian cancer.Proteomics · 2023Article
- Diagnostics and treatment of ovarian cancer in the era of precision medicine - opportunities and challenges.Frontiers in oncology · 2023Review
- "DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.Frontiers in oncology · 2023Review
- Loss of HRD functional phenotype impedes immunotherapy and can be reversed by HDAC inhibitor in ovarian cancer.International journal of biological sciences · 2023Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
objectivePoly ADP ribose polymerase inhibitors (PARPi) are most effective in BRCA1/2 mutated ovarian tumors. Better treatments are needed for homologous recombination HR-proficient cancer, including CCNE1 amplified subtypes. We have shown that histone deacetylase inhibitors (HDACi) sensitize HR-proficient ovarian cancer to PARPi. In this study, we provide complementary preclinical data for an investigator-initiated phase 1/2 clinical trial of the combination of olaparib and entinostat in recurrent, HR-proficient ovarian cancer.
methodsWe assessed the in vitro effects of the combination of olaparib and entinostat in SKOV-3, OVCAR-3 and primary cells derived from CCNE1 amplified high grade serous ovarian cancer (HGSOC) patients. We then tested the combination in a SKOV-3 xenograft model and in a patient-derived xenograft (PDX) model.
resultsEntinostat potentiates the effect of olaparib in reducing cell viability and clonogenicity of HR-proficient ovarian cancer cells. The combination reduces peritoneal metastases in a SKOV-3 xenograft model and prolongs survival in a CCNE1 amplified HR-proficient PDX model. Entinostat also enhances olaparib-induced DNA damage. Further, entinostat decreases BRCA1, a key HR repair protein, associated with decreased Ki-67, a proliferation marker, and increased cleaved PARP, a marker of apoptosis. Finally, entinostat perturbs replication fork progression, which increases genome instability.
conclusionEntinostat inhibits HR repair by reducing BRCA1 expression and stalling replication fork progression, leading to irreparable DNA damage and ultimate cell death. This work provides preclinical support for the clinical trial of the combination of olaparib and entinostat in HR-proficient ovarian cancer and suggests potential benefit even for CCNE1 amplified subtypes.
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