2021
Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity
Gayle S, Aiello R, Leelatian N, Beckta JM, Bechtold J, Bourassa P, Csengery J, Maguire RJ, Marshall D, Sundaram RK, Van Doorn J, Jones K, Moore H, Lopresti-Morrow L, Paradis T, Tylaska L, Zhang Q, Visca H, Reshetnyak YK, Andreev OA, Engelman DM, Glazer PM, Bindra RS, Paralkar VM. Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity. NAR Cancer 2021, 3: zcab021. PMID: 34316708, PMCID: PMC8210154, DOI: 10.1093/narcan/zcab021.Peer-Reviewed Original ResearchAntigen-independent mannerTherapeutic indexTumor growthSystemic toxicityHigh unmet needFavorable therapeutic indexHuman tumor modelsTopoisomerase inhibitorsSevere systemic toxicityHigh therapeutic indexRibose polymerase inhibitorsHuman solid tumorsSuppress tumor growthTumor cell killingAntibody-drug conjugatesSynergistic tumor cell killingUniversal tumorSpecific antigenSolid tumorsUnmet needPARP inhibitorsTumor modelCytotoxic payloadDNA repair inhibitorsPolymerase inhibitorsClinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas
Eder JP, Doroshow DB, T. K, Keedy VL, Sklar JS, Glazer P, Bindra R, Shapiro GI. Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas. JCO Precision Oncology 2021, 5: 466-472. PMID: 34994649, PMCID: PMC9848565, DOI: 10.1200/po.20.00247.Peer-Reviewed Original ResearchConceptsPulmonary epithelioid hemangioendotheliomaStable diseaseEpithelioid hemangioendotheliomaClinical benefitClinical benefit rateOpen-label studyPrimary end pointPoly (ADP-ribose) polymerase inhibitionDefective homologous recombination (HR) repairMesenchymal sarcomaObjective responsePartial responseClinical efficacyPatient populationBenefit rateCombination trialsPatientsSolid tumorsIDH1/2-mutant tumorsIDH1/2 mutationsPARP inhibitorsEnd pointPARP inhibitionTumorsOlaparib
2019
Unlocking PARP inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform.
Bindra R, Sundaram R, Aiello R, Marshall D, Bourassa P, Csengery J, Zhang Q, Robinson B, lopresti-Morrow L, Bechtold J, Tylaska L, Paradis T, Paralkar V, Hellsund P, Glazer P. Unlocking PARP inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform. Journal Of Clinical Oncology 2019, 37: e14664-e14664. DOI: 10.1200/jco.2019.37.15_suppl.e14664.Peer-Reviewed Original ResearchHomologous recombination deficiencyHRD statusAnti-cancer agentsClinical trialsSignificant bone marrow toxicityTumor cellsInhibitor efficacyPhase I clinical trialIND-enabling studiesDose-limiting toxicityBone marrow toxicitySignificant tumor cell killingSmall molecule anti-cancer agentNormal tissue toxicityTumor cell killingTumor-targeting approachesPARP inhibitor efficacyRelevant chemotherapyVivo tumor modelsMarrow toxicityBRCA1/2 mutationsComplete sparingBone marrowSolid tumorsChemotherapy
2001
Genomic Instability in Cancer
Rockwell S, Yuan J, Peretz S, Glazer P. Genomic Instability in Cancer. Novartis Foundation Symposia 2001, 240: 133-151. PMID: 11727926, DOI: 10.1002/0470868716.ch9.Peer-Reviewed Original ResearchConceptsGenomic instabilityChromosomal fragile sitesExposure of cellsNutrient deprivationDNA repairGenomic rearrangementsSelection pressureDNA overreplicationGene expressionGenetic changesFragile sitesGenetic heterogeneityCell proliferationGene amplificationCell populationsBenign cell populationsMutation frequencyHypoxic environmentAggressive phenotypeSolid tumorsExpressionOverreplicationCellsAdverse microenvironmentCytogenetic changes
1998
Mutagenesis induced by the tumor microenvironment
Yuan J, Glazer P. Mutagenesis induced by the tumor microenvironment. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 1998, 400: 439-446. PMID: 9685702, DOI: 10.1016/s0027-5107(98)00042-6.Peer-Reviewed Original Research