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 methodsCharacterizing genomic alterations in cancer by complementary functional associations
Kim J, Botvinnik O, Abudayyeh O, Birger C, Rosenbluh J, Shrestha Y, Abazeed M, Hammerman P, DiCara D, Konieczkowski D, Johannessen C, Liberzon A, Alizad-Rahvar A, Alexe G, Aguirre A, Ghandi M, Greulich H, Vazquez F, Weir B, Van Allen E, Tsherniak A, Shao D, Zack T, Noble M, Getz G, Beroukhim R, Garraway L, Ardakani M, Romualdi C, Sales G, Barbie D, Boehm J, Hahn W, Mesirov J, Tamayo P. Characterizing genomic alterations in cancer by complementary functional associations. Nature Biotechnology 2016, 34: 539-546. PMID: 27088724, PMCID: PMC4868596, DOI: 10.1038/nbt.3527.Peer-Reviewed Original Research