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 tumorsChemotherapyNitric oxide-donor/PARP-inhibitor combination: A new approach for sensitization to ionizing radiation
Wilson A, Menon V, Khan Z, Alam A, Litovchick L, Yakovlev V. Nitric oxide-donor/PARP-inhibitor combination: A new approach for sensitization to ionizing radiation. Redox Biology 2019, 24: 101169. PMID: 30889466, PMCID: PMC6423503, DOI: 10.1016/j.redox.2019.101169.Peer-Reviewed Original ResearchConceptsPARP inhibitorsBRCA1/2 mutationsSingle agentTumor microenvironmentAdditional therapeutic benefitBRCA1 expressionNew drug combinationsDNA-damaging therapiesNon-toxic concentrationsTumor-targeting approachesCancer patientsOvarian cancerBreast cancerDrug combinationsTherapeutic benefitClinical developmentTumorsRadiation treatmentCancerOxidative stressSubsequent inhibitionSynthetic lethality approachSensitizationHigh potencyDNA damage
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