2019
Identification of DHODH as a therapeutic target in small cell lung cancer
Li L, Ng SR, Colón CI, Drapkin BJ, Hsu PP, Li Z, Nabel CS, Lewis CA, Romero R, Mercer KL, Bhutkar A, Phat S, Myers DT, Muzumdar MD, Westcott PMK, Beytagh MC, Farago AF, Vander Heiden MG, Dyson NJ, Jacks T. Identification of DHODH as a therapeutic target in small cell lung cancer. Science Translational Medicine 2019, 11 PMID: 31694929, PMCID: PMC7401885, DOI: 10.1126/scitranslmed.aaw7852.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsBiphenyl CompoundsCarcinoma, Pancreatic DuctalCell Line, TumorDCMP DeaminaseDihydroorotate DehydrogenaseDisease ProgressionEnzyme InhibitorsHumansLung NeoplasmsMiceMolecular Targeted TherapyOxidoreductases Acting on CH-CH Group DonorsPancreatic NeoplasmsPyrimidinesSmall Cell Lung CarcinomaSurvival AnalysisXenograft Model Antitumor AssaysConceptsSmall cell lung cancerCell lung cancerPancreatic ductal adenocarcinomaLung cancerLung adenocarcinomaMouse modelSCLC cellsTherapeutic targetHuman patient-derived xenograft modelsAggressive lung cancer subtypePatient-derived xenograft modelsLung cancer subtypesAutochthonous mouse modelPotential therapeutic targetSCLC tumor growthGenetic driver eventsTreatment landscapePoor prognosisDuctal adenocarcinomaXenograft modelCancer subtypesTumor growthPharmacological inhibitionDihydroorotate dehydrogenaseGenetic vulnerability
2016
Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers
Muzumdar MD, Dorans KJ, Chung KM, Robbins R, Tammela T, Gocheva V, Li CM, Jacks T. Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers. Nature Communications 2016, 7: 12685. PMID: 27585860, PMCID: PMC5025814, DOI: 10.1038/ncomms12685.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell ProliferationCyclin-Dependent Kinase Inhibitor p16Disease ProgressionGene Expression Regulation, NeoplasticLung NeoplasmsMiceMice, TransgenicPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)Tumor Cells, CulturedTumor Suppressor Protein p53ConceptsLung adenomasLow-grade pancreatic intraepithelial neoplasiaP53 lossEarly tumor progressionPancreatic intraepithelial neoplasiaAdvanced adenocarcinomaIntraepithelial neoplasiaPancreatic tumorsP53 knockoutSolid tumorsOncogenic KrasTumor progressionSuppressive roleTumor developmentExtensive cellular heterogeneityLineage-related cellsP53AdenomasTumorsCancerContiguous growthDouble markersProgressionDistinct clonesDifferential expression