2020
Ku80-Targeted pH-Sensitive Peptide–PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation
Kaplan AR, Pham H, Liu Y, Oyaghire S, Bahal R, Engelman DM, Glazer PM. Ku80-Targeted pH-Sensitive Peptide–PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation. Molecular Cancer Research 2020, 18: 873-882. PMID: 32098827, PMCID: PMC7272299, DOI: 10.1158/1541-7786.mcr-19-0661.Peer-Reviewed Original ResearchConceptsCancer cellsTumor cellsLocal tumor irradiationTumor-selective radiosensitizationMouse tumor modelsKu80 expressionNovel agentsTumor irradiationTumor growthTumor microenvironmentTumor modelRadiation treatmentTherapeutic agentsSubcutaneous mouse tumor modelTumorsMiceCancer therapyHealthy tissueAcute toxicitySpecific targetingSelective effectPNA antisenseTumor-SelectiveAcidic culture conditionsSensitize cancer cells
2019
Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51
Kaplan AR, Gueble SE, Liu Y, Oeck S, Kim H, Yun Z, Glazer PM. Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51. Science Translational Medicine 2019, 11 PMID: 31092693, PMCID: PMC6626544, DOI: 10.1126/scitranslmed.aav4508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBRCA1 ProteinBRCA2 ProteinCell Line, TumorDNA RepairDown-RegulationE2F4 Transcription FactorFemaleGene Expression Regulation, NeoplasticHumansMice, NudePoly(ADP-ribose) Polymerase InhibitorsQuinazolinesRad51 RecombinaseReceptors, Platelet-Derived Growth FactorTumor HypoxiaVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsHomology-directed DNA repairDNA repairE2F transcription factor 4Protein phosphatase 2ATranscription factor 4DNA repair inhibitorsPhosphatase 2ARAD51 recombinaseTranscriptional corepressorMouse tumor xenograftsSynthetic lethalityGene expressionRB2/Mouse bone marrowGrowth factor receptor inhibitionRepair inhibitorsUnknown mechanismPlatelet-derived growth factor receptor inhibitionFactor 4Human tumorsInhibitor olaparibPARP inhibitorsMutationsCombination of cediranibCancer therapy
2017
A cell-penetrating antibody inhibits human RAD51 via direct binding
Turchick A, Hegan DC, Jensen RB, Glazer PM. A cell-penetrating antibody inhibits human RAD51 via direct binding. Nucleic Acids Research 2017, 45: 11782-11799. PMID: 29036688, PMCID: PMC5714174, DOI: 10.1093/nar/gkx871.Peer-Reviewed Original ResearchConceptsHomology-directed repairMolecular basisDirect bindingSynthetic lethal killingPre-clinical developmentBRCA2-deficient cancer cellsCell-penetrating antibodiesAnti-cancer agentsLupus autoantibodiesHuman Rad51DNA repairDNA bindingRAD51N-terminusCancer cellsSilico molecular modelingFunction mutationsCancer therapySpecific inhibitorDNANovel inhibitorsAttractive targetComplementarity-determining regionsMolecular modelingCell penetration