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