2025
The MATRiX trial: A multicenter, randomized, phase II study of ATR inhibition (via tuvusertib) with or without avelumab in patients with advanced anti-PD-(L)1–refractory Merkel cell carcinoma.
Bhakuni R, Hall E, Ansstas G, Bhatia S, Brohl A, Burgess M, Dimitrova M, Gao L, Ishizuka J, Lipson E, Lutzky J, Silk A, Yun J, Brownell I, Murray J, Mowery Y, Gooley T, Gore S, Topalian S, Nghiem P. The MATRiX trial: A multicenter, randomized, phase II study of ATR inhibition (via tuvusertib) with or without avelumab in patients with advanced anti-PD-(L)1–refractory Merkel cell carcinoma. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.tps9598.Peer-Reviewed Original ResearchMerkel cell carcinomaProgression-free survivalCell carcinomaProgressive diseaseATR inhibitionDay 1PD-1 pathway inhibitorsRare neuroendocrine skin cancerRecommended phase II doseAnti-tumor immune responseTreatment-emergent adverse eventsKi-67 proliferative indexPD-(L)1 blockadePhase II doseResponse Evaluation CriteriaPhase II studySolid tumor immunotherapyInduce tumor regressionNeuroendocrine skin cancerPhase I trialLog-rank testMerkel cell polyomavirusHigh response rateCell cycle checkpoint regulationII doseThe cold immunological landscape of ATM-deficient cancers
Sinha S, Ng V, Novaj A, Zhu Y, Yazaki S, Pei X, Derakhshan F, Pareja F, Setton J, Naulin F, Beltrán-Visiedo M, Shin E, Longhini A, Gardner R, Ma J, Ma K, Roulston A, Morris S, Koehler M, Powell S, Rosen E, Galluzzi L, Reis-Filho J, Khan A, Riaz N. The cold immunological landscape of ATM-deficient cancers. Journal For ImmunoTherapy Of Cancer 2025, 13: e010548. PMID: 40350205, PMCID: PMC12067784, DOI: 10.1136/jitc-2024-010548.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCheckpoint blockadeTumor immunogenicityCell infiltrationLung cancerResponse to immune checkpoint blockadeNull tumorsATR inhibitionImmune effector cell infiltrationDesign of novel combination therapiesI interferonATM-deficient cancersEffector cell infiltrationEnhance tumor immunogenicityIncreasing tumor antigenicityNovel combination therapiesImmune cell infiltrationImmune cell recruitmentTriple-negative breastType I IFN signalingActivity of etoposideSynthetic lethal strategyActivation of type I interferonDefective DNA repairType I interferon
2023
ATR protects centromere identity by promoting DAXX association with PML nuclear bodies
Trier I, Black E, Joo Y, Kabeche L. ATR protects centromere identity by promoting DAXX association with PML nuclear bodies. Cell Reports 2023, 42: 112495. PMID: 37163376, DOI: 10.1016/j.celrep.2023.112495.Peer-Reviewed Original ResearchConceptsCentromere identityInterphase centromeresNuclear bodiesDNA damage-independent mannerPromyelocytic leukemia nuclear bodiesMitotic chromosome segregationCentromere protein AATR inhibitionDNA damage responsePML nuclear bodiesATR-dependent phosphorylationAcute ATR inhibitionChaperone DAXXGenome stabilityChromosome segregationPML-NBsDamage responseUnperturbed cellsMaster regulatorAtaxia telangiectasiaC-terminusFormation defectsCentromeresCENPAberrant increase
2018
Radio-sensitizing effects of VE-821 and beyond: Distinct phosphoproteomic and metabolomic changes after ATR inhibition in irradiated MOLT-4 cells
Šalovská B, Janečková H, Fabrik I, Karlíková R, Čecháková L, Ondrej M, Link M, Friedecký D, Tichý A. Radio-sensitizing effects of VE-821 and beyond: Distinct phosphoproteomic and metabolomic changes after ATR inhibition in irradiated MOLT-4 cells. PLOS ONE 2018, 13: e0199349. PMID: 30001349, PMCID: PMC6042708, DOI: 10.1371/journal.pone.0199349.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAtaxia Telangiectasia Mutated ProteinsBinding SitesBiomarkersCell Cycle CheckpointsCell Line, TumorComputational BiologyGamma RaysGene OntologyHumansMetabolomeMetabolomicsPhosphoproteinsPhosphorylationProtein BindingProtein Kinase InhibitorsProteomeProteomicsPyrazinesRadiation ToleranceRadiation-Sensitizing AgentsSignal TransductionSulfonesTOR Serine-Threonine KinasesConceptsVE-821MOLT-4 cellsCellular metabolismOncogene-induced replication stressATR inhibitionATM-deficient cellsDNA damage responseATR/Chk1 pathwayCell biology techniquesDownregulation of mTORAnti-cancer strategyCurrent anti-cancer strategiesReplication stressPhosphorylation sitesDamage responseIrradiation-induced oxidative stressQuantitative proteomicsDNA repairChk1 pathwayCellular eventsBiology techniquesSpecific inhibitorMain regulatorTumor-specific abnormalitiesMTOR inhibition
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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