2020
A CRISPR Competition Assay to Identify Cancer Genetic Dependencies.
Girish V, Sheltzer JM. A CRISPR Competition Assay to Identify Cancer Genetic Dependencies. Bio-protocol 2020, 10: e3682. PMID: 33659353, PMCID: PMC7842800, DOI: 10.21769/bioprotoc.3682.Peer-Reviewed Original ResearchGenetic dependenciesTargeted locusCancer cell fitnessCRISPR/Cas9 systemGene of interestWhole-genome screenAnti-cancer drug developmentCell fitnessNuclease Cas9Mammalian cellsGenome editingGene dependenciesCas9 systemSpecific genesConsequences of lossCompetition assaysCell linesPotential targetGenesLociCancer typesDrug developmentFunction perturbationsCas9CRISPR
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 pairs
2018
Systematic identification of mutations and copy number alterations associated with cancer patient prognosis
Smith J, Sheltzer J. Systematic identification of mutations and copy number alterations associated with cancer patient prognosis. ELife 2018, 7: e39217. PMID: 30526857, PMCID: PMC6289580, DOI: 10.7554/elife.39217.Peer-Reviewed Original ResearchConceptsPatient prognosisSuccessful treatment decisionsDriver genesIndependent patient cohortsRobust prognostic biomarkerCancer patient prognosisSignificant prognostic powerSpecific therapeutic vulnerabilitiesSpecific cancer typesPatient cohortWorse outcomesDeadly malignancyPatient riskClinical riskPrognostic biomarkerTreatment decisionsPrognostic powerMolecular alterationsTherapeutic vulnerabilitiesCopy number alterationsCancer typesFocal CNAsTotal aneuploidyGenomic profilesPrognosisMELK expression correlates with tumor mitotic activity but is not required for cancer growth
Giuliano C, Lin A, Smith J, Palladino A, Sheltzer J. MELK expression correlates with tumor mitotic activity but is not required for cancer growth. ELife 2018, 7: e32838. PMID: 29417930, PMCID: PMC5805410, DOI: 10.7554/elife.32838.Peer-Reviewed Original ResearchConceptsMaternal embryonic leucine zipper kinaseTumor mitotic activityCancer typesMitotic activityPoor clinical prognosisBreast cancer cell linesPromising therapeutic targetTriple-negative breast cancer cell linesEmbryonic leucine zipper kinaseMultiple cancer typesLeucine zipper kinaseCancer cell linesCytotoxic chemotherapyAggressive diseaseCancer patientsClinical prognosisMELK expressionTherapeutic targetChemotherapy resistanceCancer growthTumor growthAcute inhibitionMELK inhibitorExpression correlatesCancer-related processes
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 ResearchConceptsMaternal 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