Featured Publications
Poly (ADP-ribose) polymerase inhibitors
Ratner ES, Sartorelli AC, Lin ZP. Poly (ADP-ribose) polymerase inhibitors. Current Opinion In Oncology 2012, 24: 564-571. PMID: 22759740, PMCID: PMC3799945, DOI: 10.1097/cco.0b013e3283564230.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerOvarian cancerOverall survivalEOC patientsPARP inhibitorsBRCA mutationsHereditary epithelial ovarian cancerLower chemotherapy response rateDNA repair defectsDeleterious BRCA1/2 mutationsPlatinum-based chemotherapyRecurrence-free survivalChemotherapy response rateRecent clinical trialsPoor overall survivalNew treatment optionsShorter survival timeSporadic epithelial ovarian cancerPoly (ADP-ribose) polymerasePoly (ADP-ribose) polymerase (PARP) inhibitorsEffect of cisplatinPARP inhibitor olaparibRecurrent diseaseClinical outcomesTherapeutic challengeIn 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 repairCombination 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 growthPredictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients
C. M, Lavi E, Altwerger G, Lin Z, Ratner E. Predictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients. PLOS ONE 2024, 19: e0305273. PMID: 38976671, PMCID: PMC11230535, DOI: 10.1371/journal.pone.0305273.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerEpithelial ovarian cancer patientsEpithelial ovarian cancer casesGene mutation signaturesPlatinum-based chemotherapyThe Cancer Genome AtlasResponse to treatmentOverall survivalGene mutationsMutational signaturesHomologous recombinationSurvival outcomesIncreased sensitivity to platinum-based chemotherapySensitivity to platinum-based chemotherapyAssociated with increased chemoresistanceResistance to platinum-based chemotherapySurvival timeSurvival rateFavorable response to treatmentPlatinum-induced DNA damageKaplan-Meier survival analysisPrediction of survival outcomesOvarian cancer patientsOverall survival ratePrediction of treatment outcome
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
MK-2206 sensitizes BRCA-deficient epithelial ovarian adenocarcinoma to cisplatin and olaparib
Whicker ME, Lin ZP, Hanna R, Sartorelli AC, Ratner ES. MK-2206 sensitizes BRCA-deficient epithelial ovarian adenocarcinoma to cisplatin and olaparib. BMC Cancer 2016, 16: 550. PMID: 27465688, PMCID: PMC4964088, DOI: 10.1186/s12885-016-2598-1.Peer-Reviewed Original ResearchMeSH KeywordsBRCA1 ProteinCarcinoma, Ovarian EpithelialCell Line, TumorCell SurvivalCisplatinDrug SynergismFemaleGene Expression Regulation, NeoplasticHeterocyclic Compounds, 3-RingHumansMutationNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhosphorylationPhthalazinesPiperazinesProto-Oncogene Proteins c-aktConceptsEpithelial ovarian cancerOlaparib therapyOvarian adenocarcinomaPhase II trialGreater clinical responseSerous ovarian adenocarcinomaPhospho-AKT activityAgent-induced DNA damageAkt activityEpithelial ovarian adenocarcinomaII trialPeritoneal cancerClinical responseInhibition of AktPatient populationStrong synergismFallopian tubeOvarian cancerHomologous recombination repair pathwaySame patientChemosensitization agentsClinical investigationChemoresistant cellsPlatinum resistanceBRCA-deficient cellsTriapine 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