2024
Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition
Rackear M, Quijano E, Ianniello Z, Colón-Ríos D, Krysztofiak A, Abdullah R, Liu Y, Rogers F, Ludwig D, Dwivedi R, Bleichert F, Glazer P. Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition. Oncotarget 2024, 15: 699-713. PMID: 39352803, PMCID: PMC11444335, DOI: 10.18632/oncotarget.28651.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalCell Line, TumorCell-Penetrating PeptidesHumansMiceNeoplasmsRad51 RecombinaseXenograft Model Antitumor AssaysConceptsTumor targetingMonoclonal antibody therapyTumor-specific targetingCell uptakeNucleic acid bindingCell surface antigensAntibody therapyHuman variantsClinical successCell-penetrating antibodiesAcid bindingSystemic administrationSurface antigensTumorRAD51 inhibitionAntibody platformMechanism of cell penetrationBind RAD51AntibodiesFull-lengthSpecific targetsCell penetrationDisease targetsCellsAutoantibodies
2021
Cooperation between oncogenic Ras and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance
Dong YL, Vadla GP, Lu J, Ahmad V, Klein TJ, Liu LF, Glazer PM, Xu T, Chabu CY. Cooperation between oncogenic Ras and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance. Communications Biology 2021, 4: 374. PMID: 33742110, PMCID: PMC7979758, DOI: 10.1038/s42003-021-01898-5.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAnimalsAnimals, Genetically ModifiedCell ProliferationCytokinesDrosophila melanogasterDrosophila ProteinsFemaleGene Expression Regulation, NeoplasticGenes, rasHumansJanus KinasesLung NeoplasmsMaleMice, NudeMice, TransgenicParacrine CommunicationRadiation ToleranceSignal TransductionSTAT Transcription FactorsTumor BurdenTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsTumor microenvironmentTumor radioresistanceRas clonesOncogenic Ras mutationsClinical outcomesRA tissuesCancer patientsJAK/STATRadiation therapyRobust tumorOncogenic RasTherapy outcomeTumor resistanceTumor tissueRas mutationsTumor cellsJAK/OutcomesRadioresistanceCellular responsesTissueCell-cell interactionsPatientsCytokinesRadiotherapy
2020
Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway
Lu Y, Liu Y, Oeck S, Zhang GJ, Schramm A, Glazer PM. Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway. Cancer Research 2020, 80: 4655-4667. PMID: 32873635, PMCID: PMC7642024, DOI: 10.1158/0008-5472.can-20-1192.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAniline CompoundsAnimalsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell HypoxiaCell Line, TumorDrug Resistance, NeoplasmHumansLung NeoplasmsMAP Kinase Signaling SystemMiceProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 1Up-RegulationXenograft Model Antitumor AssaysConceptsEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitorsEpithelial-mesenchymal transitionNon-small cell lung cancer (NSCLC) cell line H1975Fibroblast growth factor receptor 1 expressionMEK inhibitorsNSCLC cell line H1975EGFR-TKI resistanceEGFR-TKI osimertinibOverexpression of FGFR1Receptor 1 expressionEGFR-TKI sensitivityExpression of FGFR1Lung cancer cellsAttractive therapeutic strategyMAPK pathwayProapoptotic factor BimClinical efficacyConventional therapyDevelopment of resistanceEGFR mutationsSelective small molecule inhibitorsTKI resistanceKnockdown of FGFR1Therapeutic strategiesKu80-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
2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity
Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 2017, 9 PMID: 28148839, PMCID: PMC5435119, DOI: 10.1126/scitranslmed.aal2463.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1PARP inhibitor sensitivityPossible therapeutic strategiesHomologous recombination defectsTherapeutic strategiesTumor xenograftsInhibitor sensitivityPathologic processesSmall molecule inhibitorsIDH1/2 mutationsTumor progressionIDH2 mutationsMutant IDHPolymerase inhibitorsGlioma cellsTumor cellsHR deficiencyPARP inhibitionIDH mutationsInhibitory effectDehydrogenase 1Neomorphic activityMutant IDH1 enzymeDependent dioxygenasesMutant cells