Featured Publications
In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer
Lin ZP, Al Zouabi NN, Xu ML, Bowen NE, Wu TL, Lavi ES, Huang PH, Zhu YL, Kim B, Ratner ES. In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer. Scientific Reports 2021, 11: 8042. PMID: 33850183, PMCID: PMC8044145, DOI: 10.1038/s41598-021-87325-5.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerSmall molecule inhibitorsPARP inhibitor resistancePARP inhibitorsBRCA mutationsOvarian cancerEOC cellsPoly ADP-ribose polymerase inhibitorsMolecule inhibitorsInhibitor resistanceADP-ribose polymerase inhibitorsTumor-bearing miceNovel small molecule inhibitorPARP inhibitor olaparibDefective homologous recombination (HR) repairEOC xenograftsClinical efficacySurvival timePutative small molecule inhibitorsInhibitor olaparibPolymerase inhibitorsHR repairInhibitorsCancerHomologous recombination repairTriapine Disrupts CtIP-Mediated Homologous Recombination Repair and Sensitizes Ovarian Cancer Cells to PARP and Topoisomerase Inhibitors
Lin ZP, Ratner ES, Whicker ME, Lee Y, Sartorelli AC. Triapine Disrupts CtIP-Mediated Homologous Recombination Repair and Sensitizes Ovarian Cancer Cells to PARP and Topoisomerase Inhibitors. Molecular Cancer Research 2014, 12: 381-393. PMID: 24413181, PMCID: PMC3962722, DOI: 10.1158/1541-7786.mcr-13-0480.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialCarrier ProteinsCell Line, TumorDrug SynergismFemaleHumansNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesPyridinesRecombination, GeneticRecombinational DNA RepairThiosemicarbazonesTopoisomerase InhibitorsTransfectionConceptsHomologous recombination repairEOC cellsCtIP phosphorylationRecombination repairDNA double-strand break resectionCyclin-dependent kinase activityTopoisomerase II inhibitor etoposidePhosphorylation of CtIPDouble-strand break resectionSmall molecule inhibitorsRPA32 phosphorylationBRCA1 interactionBRCA1 fociNbs1 complexMre11-Rad50Chk1 activationDSB resectionKinase activitySynthetic lethalityRAD51 fociOvarian cancer cellsInhibitor etoposideCell cycleRibonucleotide reductaseCtIPCombination of triapine, olaparib, and cediranib suppresses progression of BRCA-wild type and PARP inhibitor-resistant epithelial ovarian cancer
Lin ZP, Zhu YL, Lo YC, Moscarelli J, Xiong A, Korayem Y, Huang PH, Giri S, LoRusso P, Ratner ES. Combination of triapine, olaparib, and cediranib suppresses progression of BRCA-wild type and PARP inhibitor-resistant epithelial ovarian cancer. PLOS ONE 2018, 13: e0207399. PMID: 30444904, PMCID: PMC6239325, DOI: 10.1371/journal.pone.0207399.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBRCA1 ProteinBreast NeoplasmsCell Line, TumorDrug Resistance, NeoplasmFemaleHumansMice, NudeMice, SCIDPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPyridinesQuinazolinesThiosemicarbazonesXenograft Model Antitumor AssaysConceptsEpithelial ovarian cancerBRCA wild typeSCID-beige miceXenograft mouse modelOvarian cancerMouse modelSurvival timeNude micePARP inhibitorsEOC cell linesPARP inhibitor olaparibHomologous recombination repairCombination regimentsDefective homologous recombination (HR) repairEOC growthC tumorsSignificant prolongationBRCA mutationsAbdominal circumferenceEOC cellsSingle drugCediranibMarked suppressionTriple combinationTumor growth
2023
Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib
Roberts C, Rojas-Alexandre M, Hanna R, Lin Z, Ratner E. Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib. Cancers 2023, 15: 3919. PMID: 37568736, PMCID: PMC10417836, DOI: 10.3390/cancers15153919.Peer-Reviewed Original ResearchEpithelial ovarian cancerRepair gene expressionPARP inhibitorsHomologous recombinationGene expressionDNA repair gene expressionCancer cellsLethal gynecologic malignancyDrug-resistant recurrenceDownregulation of genesOvarian cancer cellsGrowth factor betaWild-type cancer cellsDose-dependent mannerDNA repair genesGynecologic malignanciesMesenchymal tumorsOvarian tumorsEpithelial cell lineOvarian cancerMetastatic spreadClinical utilityEOC cellsFunctions of EMTFactor beta
2016
Triapine potentiates platinum-based combination therapy by disruption of homologous recombination repair
Ratner ES, Zhu YL, Penketh PG, Berenblum J, Whicker ME, Huang PH, Lee Y, Ishiguro K, Zhu R, Sartorelli AC, Lin ZP. Triapine potentiates platinum-based combination therapy by disruption of homologous recombination repair. British Journal Of Cancer 2016, 114: 777-786. PMID: 26964031, PMCID: PMC4984868, DOI: 10.1038/bjc.2016.54.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarboplatinCarcinoma, Ovarian EpithelialCisplatinDoxorubicinDrug Resistance, NeoplasmFemaleHumansMiceMice, NudeNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesPolyethylene GlycolsRecombinational DNA RepairTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsPlatinum-based combination therapyEpithelial ovarian cancerCombination therapyWild-type cancer cellsEOC cellsPlatinum-resistant epithelial ovarian cancerPlatinum resistanceHomologous recombination repairEOC tumor growthPlatinum-based combinationsXenograft tumor mouse modelCancer cellsWild-type BRCATumor growth delayTumor mouse modelClonogenic survival assaysClinical efficacyBRCA statusOvarian cancerMouse modelTumor growthGrowth delayHRR activityTherapySurvival assays