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
2017
Survival of pancreatic cancer cells lacking KRAS function
Muzumdar MD, Chen PY, Dorans KJ, Chung KM, Bhutkar A, Hong E, Noll EM, Sprick MR, Trumpp A, Jacks T. Survival of pancreatic cancer cells lacking KRAS function. Nature Communications 2017, 8: 1090. PMID: 29061961, PMCID: PMC5653666, DOI: 10.1038/s41467-017-00942-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBenzimidazolesCarcinoma, Pancreatic DuctalDNA Copy Number VariationsHumansImmunoblottingIndazolesMiceMorpholinesPancreatic NeoplasmsPhenylurea CompoundsPiperidinesProto-Oncogene MasProto-Oncogene Proteins p21(ras)PurinesPyrimidinesPyrimidinonesQuinazolinonesSulfonamidesThiazolesConceptsMitogen-activated protein kinasePDAC cellsCRISPR/Cas-mediated genome editingDependent mitogen-activated protein kinaseKRAS inhibitionGene expression profilesMetastasis-related genesProto-oncogene KRASGenome editingProtein kinasePI3K inhibitorsExpression profilesDeficient cellsPancreatic cancer cellsMechanisms of responsePDAC resistanceKRAS functionInduced sensitivityPancreatic ductal adenocarcinomaRole of KRASK inhibitorsCancer cellsKRAS inhibitorsAbsolute dependenceSubset of humans