ArticleOncotarget2014
Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Article
- Functional and therapeutic significant of heat-shock protein 90 (HSP90) in reproductive cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Targeting HSP90 in Gynecologic Cancer: Molecular Mechanisms and Therapeutic Approaches.Cell biochemistry and biophysics · 2025Review
- Olaparib Enhances the Efficacy of Third-Generation Oncolytic Adenoviruses Against Glioblastoma by Modulating DNA Damage Response and p66shc-Induced Apoptosis.CNS neuroscience & therapeutics · 2024Article
- Homologous recombination proficient subtypes of high-grade serous ovarian cancer: treatment options for a poor prognosis group.Frontiers in oncology · 2024Review
- LCK facilitates DNA damage repair by stabilizing RAD51 and BRCA1 in the nucleus of chemoresistant ovarian cancer.Journal of ovarian research · 2023Article
- Smart Nanofiber Mesh with Locally Sustained Drug Release Enabled Synergistic Combination Therapy for Glioblastoma.Nanomaterials (Basel, Switzerland) · 2023Article
- Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents.Cancer treatment and research · 2023Review
- Effect of the PARP inhibitor veliparib on germ cell tumor cell lines.Oncology letters · 2022Article
- PARP inhibitors as single agents and in combination therapy: the most promising treatment strategies in clinical trials for BRCA-mutant ovarian and triple-negative breast cancers.Expert opinion on investigational drugs · 2022Review
- Hsp90 inhibition sensitizes DLBCL cells to cisplatin.Cancer chemotherapy and pharmacology · 2022Article
- Review
- Understanding and overcoming resistance to PARP inhibitors in cancer therapy.Nature reviews. Clinical oncology · 2021Review
- Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models.Molecular cancer therapeutics · 2021Article
- Strategies in Overcoming Homologous Recombination Proficiency and PARP Inhibitor Resistance.Molecular cancer therapeutics · 2021Review
- Identification of new target proteins of a Urotensin-II receptor antagonist using transcriptome-based drug repositioning approach.Scientific reports · 2021Article
- Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma.EBioMedicine · 2020Article
- PARP inhibitor resistance: the underlying mechanisms and clinical implications.Molecular cancer · 2020Review
- β-hCG-induced mutant BRCA1 ignites drug resistance in susceptible breast tissue.Carcinogenesis · 2019Article
- Combining PARP and CDK4/6 inhibitors in MYC driven ovarian cancer.EBioMedicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The promise of PARP-inhibitors(PARPis) in the management of epithelial ovarian cancer(EOC) is tempered by the fact that approximately 50% of patients with homologous recombination (HR)-proficient tumors do not respond well to these agents. Combination of PARPis with agents that inhibit HR may represent an effective strategy to enhance their activity in HR-proficient tumors. Using a bioinformatics approach, we identified that heat shock protein 90 inhibitors(HSP90i) may suppress HR and thus revert HR-proficient to HR-deficient tumors. Analysis of publicly available gene expression data showed that exposure of HR-proficient breast cancer cell lines to HSP90i 17-AAG(17-allylamino-17-demethoxygeldanamycin) downregulated HR, ATM and Fanconi Anemia pathways. In HR-proficient EOC cells, 17-AAG suppressed HR as assessed using the RAD51 foci formation assay and this was further confirmed using the Direct Repeat-GFP reporter assay. Furthermore, 17-AAG downregulated BRCA1 and/or RAD51 protein levels, and induced significantly more γH2AX activation in combination with olaparib compared to olaparib alone. Finally, sublethal concentrations of 17-AAG sensitized HR-proficient EOC lines to olaparib and carboplatin but did not affect sensitivity of the HR-deficient OVCAR8 line arguing that the 17-AAG mediated sensitization is dependent on suppression of HR. These results provide a preclinical rationale for using a combination of olaparib/17-AAG in HR-proficient EOC.
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