2016
DiSCoVERing Innovative Therapies for Rare Tumors: Combining Genetically Accurate Disease Models with In Silico Analysis to Identify Novel Therapeutic Targets
Hanaford A, Archer T, Price A, Kahlert U, Maciaczyk J, Nikkhah G, Kim J, Ehrenberger T, Clemons P, Dančík V, Seashore-Ludlow B, Viswanathan V, Stewart M, Rees M, Shamji A, Schreiber S, Fraenkel E, Pomeroy S, Mesirov J, Tamayo P, Eberhart C, Raabe E. DiSCoVERing Innovative Therapies for Rare Tumors: Combining Genetically Accurate Disease Models with In Silico Analysis to Identify Novel Therapeutic Targets. Clinical Cancer Research 2016, 22: 3903-3914. PMID: 27012813, PMCID: PMC5055054, DOI: 10.1158/1078-0432.ccr-15-3011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkersCell Line, TumorCerebellar NeoplasmsComputational BiologyComputer SimulationCyclin-Dependent KinasesDisease Models, AnimalDrug DiscoveryGene Expression ProfilingGenetic Predisposition to DiseaseHumansMedulloblastomaMiceModels, BiologicalNeural Stem CellsPhosphorylationPiperazinesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycPyridinesTranscriptomeTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsGroup 3 medulloblastomaProgenitor cellsHuman neural stemCyclin-dependent kinasesRare tumorHuman neural stem cell modelNeural stemGenetically accurate modelsSurvival of miceDominant-negative p53Stem cell modelPotential effective treatmentConstitutively active AktAggressive medulloblastomaDrug sensitivity datasetsDrug sensitivity databaseNovel therapeutic targetsMedulloblastoma xenograftsAccurate disease modelsHuman stemInnovative therapiesIncreased apoptosisNeural stem cell modelIn silico analysisIn silico analysis methods
2015
A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer
Wilson FH, Johannessen CM, Piccioni F, Tamayo P, Kim JW, Van Allen EM, Corsello SM, Capelletti M, Calles A, Butaney M, Sharifnia T, Gabriel SB, Mesirov JP, Hahn WC, Engelman JA, Meyerson M, Root DE, Jänne PA, Garraway LA. A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer. Cancer Cell 2015, 27: 397-408. PMID: 25759024, PMCID: PMC4398996, DOI: 10.1016/j.ccell.2015.02.005.Peer-Reviewed Original ResearchConceptsFunctional genetic studiesG protein-coupled receptorsResistance driversALK inhibitionFunctional landscapeGenetic studiesLung cancer cellsALK inhibitor resistanceResistance pathwaysMechanisms of resistanceReceptor familyPKC activationPurinergic receptor familyPKC inhibitionCrizotinib-resistant ALKCancer cellsInhibitor resistanceGene signatureDependent mechanismLung cancerLung tumorsALK inhibitorsInhibitionALKMechanism
2014
A Melanoma Cell State Distinction Influences Sensitivity to MAPK Pathway Inhibitors
Konieczkowski D, Johannessen C, Abudayyeh O, Kim J, Cooper Z, Piris A, Frederick D, Barzily-Rokni M, Straussman R, Haq R, Fisher D, Mesirov J, Hahn W, Flaherty K, Wargo J, Tamayo P, Garraway L. A Melanoma Cell State Distinction Influences Sensitivity to MAPK Pathway Inhibitors. Cancer Discovery 2014, 4: 816-827. PMID: 24771846, PMCID: PMC4154497, DOI: 10.1158/2159-8290.cd-13-0424.Peer-Reviewed Original ResearchMeSH KeywordsAnilidesBenzimidazolesBenzocycloheptenesCell Line, TumorCells, CulturedDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHepatocyte Growth FactorHumansIndolesMAP Kinase Signaling SystemMelanocytesMelanomaMicrophthalmia-Associated Transcription FactorNF-kappa B p50 SubunitProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-metPyridinesQuinolinesSulfonamidesTriazolesConceptsBRAF(V600)-mutant melanomaMAPK pathway inhibitorsNF-kB activationPathway inhibitorNF-kBMelanocyte lineage transcription factor MITFCell linesDrug-sensitive cell linesResistance to MAPK pathway inhibitorsMITF expressionReceptor tyrosine kinase AXLTranscription factor MITFTyrosine kinase AXLResistance marker genesResistant cell linesNF-kB signalingResistant to inhibitionClinical benefitPatient biopsiesMEK inhibitorsTranscriptional profilesOncogenic BRAF(V600EDrug resistanceInhibitor sensitivityCell states