2024
A TRilogy of ATR’s Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer
Joo Y, Ramirez C, Kabeche L. A TRilogy of ATR’s Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer. Cancers 2024, 16: 3536. PMID: 39456630, PMCID: PMC11506335, DOI: 10.3390/cancers16203536.Peer-Reviewed Original ResearchDNA damage responseNon-canonical rolesCell cyclePromote faithful chromosome segregationDetect mechanical forcesDNA damage response pathwayFaithful chromosome segregationDNA damage checkpointRad3-related proteinNuclear membrane integrityCancer therapy targetATR inhibitorsChromosome segregationDamage checkpointDamage responseApical kinaseDamaged DNAMembrane integrityAtaxia telangiectasiaNon-canonicalCancer cellsDNAClinical trialsCancer therapyClinical relevance632P Results from the first-in-human study of ATR inhibitor, IMP9064 monotherapy dose escalation in patients with advanced solid tumors
Lin C, Schneider R, Gutierrez M, Shen L, Chung K, Doroshow D, Gao B, Millward M, Hsieh C, Xu C, Cai S, Tian Y, Liu L, Shen C, Tan Y, He Y, Zhang C, Li L, Ma M, Xu L. 632P Results from the first-in-human study of ATR inhibitor, IMP9064 monotherapy dose escalation in patients with advanced solid tumors. Annals Of Oncology 2024, 35: s503-s504. DOI: 10.1016/j.annonc.2024.08.699.Peer-Reviewed Original ResearchA phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation.
Heumann T, Stockton S, Cecchini M, Aljumaily R, Shyr C, Whisenant J, Starr J, Dayyani F, Baranda J, Trikalinos N, Ivy S, LoRusso P, Das S, Gore S, Beumer J, Berlin J. A phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation. Journal Of Clinical Oncology 2024, 42: 3077-3077. DOI: 10.1200/jco.2024.42.16_suppl.3077.Peer-Reviewed Original ResearchAdvanced solid tumorsMaximum tolerated doseDose escalationSolid tumorsPhase I study of irinotecanRecommended phase 2 doseRefractory advanced solid tumorsPhase 2 dosePhase I studyAnti-tumor activityBiweekly irinotecanInhibitor irinotecanIrinotecan exposureWeekly irinotecanTolerated doseDosing scheduleCancer xenograftsAdult patientsIrinotecanAssess safetyATR inhibitorsElimusertibSecondary objectivesDoseStandard care
2023
ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei
Joo Y, Black E, Trier I, Haakma W, Zou L, Kabeche L. ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei. Molecular Cell 2023, 83: 3642-3658.e4. PMID: 37788673, PMCID: PMC10599252, DOI: 10.1016/j.molcel.2023.09.003.Peer-Reviewed Original ResearchConceptsATR inhibitorsLamin A/CCytoplasmic DNA sensor cGASHuman ataxia telangiectasiaDNA sensor cGASCdk1 phosphorylationGenomic integrityKinase functionMicronuclear DNAAtaxia telangiectasiaCDK1 inhibitionChromosomal instabilityS phaseAutonomous mechanismsAutophagosome accumulationATRCancer cellsDNACell populationsCGASCellsMicronucleiRad3GenomeChromothripsis
2022
TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor.
Jo U, Murai Y, Agama KK, Sun Y, Saha LK, Yang X, Arakawa Y, Gayle S, Jones K, Paralkar V, Sundaram RK, Van Doorn J, Vasquez JC, Bindra RS, Choi WS, Pommier Y. TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor. Molecular Cancer Therapeutics 2022, 21: 1090-1102. PMID: 35439320, PMCID: PMC9256811, DOI: 10.1158/1535-7163.mct-21-1000.Peer-Reviewed Original ResearchConceptsATR inhibitorsTop1 inhibitorsHomologous recombination deficiencyNovel molecular interactionApoptotic cell deathCancer cellsTop1 cleavage complexesAtaxia telangiectasiaCleavage complexesCell deathDNA damageHigher DNA damageMolecular interactionsDNA baseKinase inhibitorsI inhibitorMolecular pharmacologyMouse xenograftsTOP1Recombination deficiencyTopoisomerase I inhibitorInhibitorsTumor growthRad3Predictive biomarkers
2017
Targeting ATR in cancer medicine
Sundar R, Brown J, Russo A, Yap T. Targeting ATR in cancer medicine. Current Problems In Cancer 2017, 41: 302-315. PMID: 28662958, DOI: 10.1016/j.currproblcancer.2017.05.002.Peer-Reviewed Educational MaterialsPoly(ADP-ribose) polymerase inhibitorsATR inhibitorsDNA damage responsePolymerase inhibitorsEarly-phase clinical trialsAtaxia telangiectasiaImmune checkpoint inhibitorsBiomarkers of responseCheckpoint inhibitorsDNA damagePreclinical dataCombinatorial regimensPatient selectionReplication-associated DNA damageAntitumor strategyCell cycle checkpoint signalingClinical developmentRepair of replication-associated DNA damagePreclinical biologyTargeting ATRAntitumor therapyATR inhibitionSingle agentCell cycle checkpointsClinical trials
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