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
2011
Reduced Level of Ribonucleotide Reductase R2 Subunits Increases Dependence on Homologous Recombination Repair of Cisplatin-Induced DNA Damage
Lin ZP, Lee Y, Lin F, Belcourt MF, Li P, Cory JG, Glazer PM, Sartorelli AC. Reduced Level of Ribonucleotide Reductase R2 Subunits Increases Dependence on Homologous Recombination Repair of Cisplatin-Induced DNA Damage. Molecular Pharmacology 2011, 80: 1000-1012. PMID: 21875941, PMCID: PMC3228527, DOI: 10.1124/mol.111.074708.Peer-Reviewed Original ResearchConceptsNucleotide excision repairHomologous recombination repairR2 subunitRibonucleotide reductaseRecombination repairCell cycleP53-deficient human colon cancer cellsDNA damageS phaseDepletion of BRCA1Mammalian ribonucleotide reductaseSubsequent S phaseDouble-strand breaksHuman colon cancer cellsP53-deficient cancer cellsSingle-strand gapsCancer cellsCisplatin-induced DNA damageColon cancer cellsCisplatin-DNA lesionsGap-filling synthesisHeteromeric enzymeReplication stressΓ-H2AX inductionDNA repair
2006
Excess ribonucleotide reductase R2 subunits coordinate the S phase checkpoint to facilitate DNA damage repair and recovery from replication stress
Lin ZP, Belcourt MF, Carbone R, Eaton JS, Penketh PG, Shadel GS, Cory JG, Sartorelli AC. Excess ribonucleotide reductase R2 subunits coordinate the S phase checkpoint to facilitate DNA damage repair and recovery from replication stress. Biochemical Pharmacology 2006, 73: 760-772. PMID: 17188250, DOI: 10.1016/j.bcp.2006.11.014.Peer-Reviewed Original Research
2004
Stable Suppression of the R2 Subunit of Ribonucleotide Reductase by R2-targeted Short Interference RNA Sensitizes p53(–/–) HCT-116 Colon Cancer Cells to DNA-damaging Agents and Ribonucleotide Reductase Inhibitors*
Lin ZP, Belcourt MF, Cory JG, Sartorelli AC. Stable Suppression of the R2 Subunit of Ribonucleotide Reductase by R2-targeted Short Interference RNA Sensitizes p53(–/–) HCT-116 Colon Cancer Cells to DNA-damaging Agents and Ribonucleotide Reductase Inhibitors*. Journal Of Biological Chemistry 2004, 279: 27030-27038. PMID: 15096505, DOI: 10.1074/jbc.m402056200.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCell Line, TumorCell SurvivalCisplatinColonic NeoplasmsDeoxyribonucleotidesDNA DamageDown-RegulationDoxorubicinEnzyme InhibitorsEtoposideGene Expression Regulation, NeoplasticGene SilencingHumansHydroxyureaIntracellular Signaling Peptides and ProteinsProtein SubunitsProto-Oncogene ProteinsPyridinesRecombinant ProteinsRibonucleotide ReductasesRNA, Small InterferingThiosemicarbazonesTumor Suppressor Protein p53VincristineConceptsShort interference RNAR2 proteinRibonucleotide reductaseInterference RNADNA damageRNR inhibitorsHCT-116 cellsMammalian ribonucleotide reductaseDNA-damaging agent cisplatinCellular growth rateHCT-116 colon cancer cellsDNA-damaging agentsP53-dependent inductionColon cancer cellsHCT-116 human colon carcinoma cellsHuman colon carcinoma cellsDNA replicationEctopic expressionKnockdown cellsColon carcinoma cellsExpression vectorDeoxyribonucleoside diphosphatesStable expressionR2 subunitRibonucleotide reductase inhibitor