2019
Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials
Lin A, Giuliano CJ, Palladino A, John KM, Abramowicz C, Yuan ML, Sausville EL, Lukow DA, Liu L, Chait AR, Galluzzo ZC, Tucker C, Sheltzer JM. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Science Translational Medicine 2019, 11 PMID: 31511426, PMCID: PMC7717492, DOI: 10.1126/scitranslmed.aaw8412.Peer-Reviewed Original ResearchConceptsClinical trialsCancer drugsDose-limiting toxicityLack of efficacyDrug Administration approvalNumber of therapiesCancer cell proliferationMultiple cancer typesMechanism of actionClinical benefitAdministration approvalCommon causeTrial failuresSmall molecule inhibitorsClinical testingCDK11 expressionHuman patientsPreclinical settingCancer typesU.S. FoodTarget toxicityNew drugsDrugsCell proliferationDrug-indication pairsGenerating Single Cell–Derived Knockout Clones in Mammalian Cells with CRISPR/Cas9
Giuliano CJ, Lin A, Girish V, Sheltzer JM. Generating Single Cell–Derived Knockout Clones in Mammalian Cells with CRISPR/Cas9. Current Protocols In Molecular Biology 2019, 128: e100. PMID: 31503414, PMCID: PMC6741428, DOI: 10.1002/cpmb.100.Peer-Reviewed Original ResearchConceptsKnockout clonesMammalian cellsCell linesCRISPR/Cas9 technologyGuide RNA designMammalian cell linesGene lossClonal cell linesGene functionProtein functionGene targetingNew cell lineCas9 technologyTargeted geneFunction mutationsInterclonal heterogeneityRNA designSingle cellsSuccessful derivationClonesCRISPRCRISPR deliveryBiological reagentsRapid generationMutations
2017
CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials
Lin A, Giuliano C, Sayles N, Sheltzer J. CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials. ELife 2017, 6: e24179. PMID: 28337968, PMCID: PMC5365317, DOI: 10.7554/elife.24179.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCell SurvivalCRISPR-Cas SystemsGene Knockout TechniquesGene TargetingHumansMutagenesisProtein Serine-Threonine KinasesConceptsMaternal embryonic leucine zipper kinaseClinical trialsCancer cell linesBasal breast cancer cell linesCancer typesCell linesNovel chemotherapy agentsTriple-negative subtypeCurrent clinical trialsBreast cancer cell linesEmbryonic leucine zipper kinaseLeucine zipper kinaseMELK knockdownBreast cancerChemotherapy agentsPreclinical resultsSmall molecule inhibitorsAnchorage-independent growthMELK inhibitorTarget mechanismsPreclinical target validationTrialsDoubling timeTarget validationInhibitors