2021
Protein neddylation as a therapeutic target in pulmonary and extrapulmonary small cell carcinomas
Norton J, Augert A, Eastwood E, Basom R, Rudin C, MacPherson D. Protein neddylation as a therapeutic target in pulmonary and extrapulmonary small cell carcinomas. Genes & Development 2021, 35: 870-887. PMID: 34016692, PMCID: PMC8168556, DOI: 10.1101/gad.348316.121.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Transcription FactorsCarcinoma, Small CellCell DeathCell Line, TumorCOP9 Signalosome ComplexCyclopentanesDisease Models, AnimalGene Expression Regulation, NeoplasticHeterograftsHumansLung NeoplasmsMiceNEDD8 ProteinNeuroendocrine CellsProteinsPyrimidinesRepressor ProteinsSequence DeletionConceptsSmall cell lung carcinomaSmall cell carcinomaExtrapulmonary small cell carcinomaNeddylation inhibitionCell carcinomaCell statesGenome-scale CRISPR/Therapeutic targetPatient-derived xenograft modelsCell linesDeletion of componentsSolid tumor malignanciesCell lung carcinomaNovel therapeutic approachesPotential therapeutic targetSuppressor screenSCLC cell linesCOP9 signalosomeProtein neddylationCRISPR/Genetic suppressionPathway genesPDX modelsMajor regulatorLung carcinoma
2019
Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition
Augert A, Eastwood E, Ibrahim A, Wu N, Grunblatt E, Basom R, Liggitt D, Eaton K, Martins R, Poirier J, Rudin C, Milletti F, Cheng W, Mack F, MacPherson D. Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition. Science Signaling 2019, 12 PMID: 30723171, PMCID: PMC6530478, DOI: 10.1126/scisignal.aau2922.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Transcription FactorsCell Line, TumorEnzyme InhibitorsGene Expression Regulation, NeoplasticHistone DemethylasesHumansKaplan-Meier EstimateLung NeoplasmsMice, Inbred NODMice, KnockoutMice, SCIDReceptors, NotchSignal TransductionSmall Cell Lung CarcinomaTumor BurdenXenograft Model Antitumor AssaysConceptsSmall cell lung cancerCell lung cancerNonsmall cell lung cancerLung cancerNotch activationLSD1 inhibitionPatient-derived xenograft modelsLSD1 inhibitorsReactivation of NotchFirst-line standardExpression of Ascl1Durable tumor regressionTranscription factor Ascl1Notch pathway activationLineage genesKnockdown studiesNotch pathwayDownstream signalingCare treatmentPDX modelsTumor regressionTargeted therapySCLC tumorigenesisActionable mutationsXenograft model