2024
The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma
McCord M, Sears T, Wang W, Chaliparambil R, An S, Sarkaria J, James C, Ruggeri B, Gueble S, Bindra R, Horbinski C. The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma. Neuro-Oncology 2024, noae257. PMID: 39658092, DOI: 10.1093/neuonc/noae257.Peer-Reviewed Original ResearchMedian survival of miceSurvival of miceMedian survivalIDH wild-type glioblastomaO-6-methylguanine-DNA methyltransferaseExposure to temozolomideAcquired resistance to TMZWild-type glioblastomaPatient-derived xenograftsSensitivity to temozolomidePatient-derived modelsResistance to temozolomideLN229 glioma cellsPatient-derived glioblastomaRecurrent tumorsMGMT deficiencyFractionated RTTemozolomideLow dosesImprove outcomesGlioblastomaEnzyme deficiencyMismatch repairGlioma cellsGBM12O6-Guanine Targeting Novel DNA Cross-Linker and ATR Inhibitor Combination for MGMT-Silenced IDH1/2 Mutant Acute Myeloid Leukemia
Bhardwaj P, Sundaram R, Friedman S, Baassiri A, Matthews M, VanOudenhove J, Gueble S, Halene S, Bindra R. O6-Guanine Targeting Novel DNA Cross-Linker and ATR Inhibitor Combination for MGMT-Silenced IDH1/2 Mutant Acute Myeloid Leukemia. Blood 2024, 144: 6130. DOI: 10.1182/blood-2024-210621.Peer-Reviewed Original ResearchAML patient samplesHematologic adverse effectsMGMT promoter hypermethylationPatient-derived xenograftsDe novoMismatch repairO6 position of guaninePromoter hypermethylationMyelodysplastic syndromeRNA-seq analysisMyeloid leukemiaATR inhibitorsDNA repair proteinsClinical trialsSelection of mutationsFunctional mismatch repairPatient samplesMutant acute myeloid leukemiaBiomarker-targeted therapiesCell line pairsAlkylation DNA damageMutant IDH1/2 inhibitorsRNA-seqCases of AMLMGMT promoter methylation
2017
Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells
Scanlon SE, Scanlon CD, Hegan DC, Sulkowski PL, Glazer PM. Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells. Carcinogenesis 2017, 38: 627-637. PMID: 28472268, PMCID: PMC5862357, DOI: 10.1093/carcin/bgx038.Peer-Reviewed Original ResearchConceptsHomology-dependent DNA double-strand break repairDNA repair pathwaysRepair pathwaysHigh-fidelity DNA repair pathwayDNA double-strand break repairMismatch repairDouble-strand break repairDNA double-strand breaksGlobal transcriptional patternsDNA repair proteinsRadiation-induced DNA double-strand breaksDouble-strand breaksTranscriptional repressionDirect DNA damageHost-cell reactivation assayEpigenetic remodelingTranscriptional patternsTranscriptional changesBreak repairDNA mutagenesisGenomic instabilityRepair proteinsHeavy metals nickelLung cellsTumor growth
2015
Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment
Scanlon SE, Glazer PM. Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment. DNA Repair 2015, 32: 180-189. PMID: 25956861, PMCID: PMC4522377, DOI: 10.1016/j.dnarep.2015.04.030.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDNA repair pathwaysRepair pathwaysDNA repairCertain DNA repair genesMost DNA repair pathwaysDNA double-strand break repairDouble-strand break repairPost-translational modificationsNucleotide excision repairDNA repair genesTumor suppressor geneMultifaceted controlTranslational downregulationEpigenetic levelBreak repairMutator phenotypeCellular consequencesGenomic instabilityExcision repairHypoxic cancer cellsSuppressor geneIntra-tumor heterogeneityMismatch repairPersistent silencingDNA damage
2013
Hypoxia and DNA repair.
Glazer PM, Hegan DC, Lu Y, Czochor J, Scanlon SE. Hypoxia and DNA repair. The Yale Journal Of Biology And Medicine 2013, 86: 443-51. PMID: 24348208, PMCID: PMC3848098.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDNA repairHomology-dependent repairDNA repair pathwaysNucleotide excision repairDNA mismatch repairGenomic integrityDependent repairCell physiologyRepair pathwaysExcision repairHypoxic cancer cellsCell metabolismGenetic instabilityMismatch repairInduction of angiogenesisCancer progressionCell growthCancer cellsNeoplastic developmentRepairSolid tumorsKey componentHypoxiaProfound changesApoptosis