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 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 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
2020
Flow Cytometric Analyses of p53-Mediated Cell Cycle Arrest and Apoptosis in Cancer Cells
Al Zouabi NN, Roberts CM, Lin ZP, Ratner ES. Flow Cytometric Analyses of p53-Mediated Cell Cycle Arrest and Apoptosis in Cancer Cells. Methods In Molecular Biology 2020, 2255: 43-53. PMID: 34033093, DOI: 10.1007/978-1-0716-1162-3_5.Peer-Reviewed Original ResearchConceptsGene of interestCell cycle arrestCycle arrestCell typesDNA damaging agentsP53-mediated cell cycle arrestCell cycle progressionTumor suppressor p53Cellular contextEctopic expressionExogenous stressCell cycle distributionDamaging agentsCycle progressionTumor suppressorSuppressor p53Stable expressionPhenotypic analysisCell survivalCell deathGenomic damageP53 functionGenesEnvironmental insultsCycle distribution
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
2014
p53 protein aggregation promotes platinum resistance in ovarian cancer
Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V, Liang M, Romanoff E, Bingham J, Garofalo F, Alvero A, Mor G. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene 2014, 34: 3605-3616. PMID: 25263447, DOI: 10.1038/onc.2014.296.Peer-Reviewed Original ResearchConceptsPro-apoptotic functionP53 aggregationProtein aggregationP53 aggregatesNormal transcriptional activationTwo-dimensional gel electrophoresisCancer cellsCancer cell survivalKey transcriptional factorGenetic mutationsHigh-grade serous ovarian carcinomaP53 inactivationP53 proteinStem cell propertiesCancer stem cell propertiesCellular homeostasisTranscriptional activationCancer stem cellsTranscriptional factorsTumor-initiating capacityP53 turnoverCell survivalHGSOC cellsStem cellsPotential therapeutic target
2004
Age-Related Differences in Vincristine Toxicity and Biodistribution in Wild-Type and Transporter-Deficient Mice
Muramatsu T, Johnson DR, Finch RA, Johnson LK, Leffert JJ, Lin ZP, Pizzorno G, Sartorelli AC. Age-Related Differences in Vincristine Toxicity and Biodistribution in Wild-Type and Transporter-Deficient Mice. Oncology Research Featuring Preclinical And Clinical Cancer Therapeutics 2004, 14: 331-343. PMID: 15301424, DOI: 10.3727/0965040041292387.Peer-Reviewed Original Research