2023
Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor
Bhattacharjee D, Bakar J, Chitnis S, Sausville E, Ashtekar K, Mendelson B, Long K, Smith J, Heppner D, Sheltzer J. Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor. Cell Chemical Biology 2023, 30: 1211-1222.e5. PMID: 37827156, PMCID: PMC10715717, DOI: 10.1016/j.chembiol.2023.09.013.Peer-Reviewed Original Research
2022
Genome-wide identification and analysis of prognostic features in human cancers
Smith JC, Sheltzer JM. Genome-wide identification and analysis of prognostic features in human cancers. Cell Reports 2022, 38: 110569. PMID: 35354049, PMCID: PMC9042322, DOI: 10.1016/j.celrep.2022.110569.Peer-Reviewed Original ResearchConceptsAdverse biomarkersSignificant prognostic biomarkerShorter survival timePromising therapeutic targetPatient survival dataPreclinical cancer researchPrognostic featuresAggressive malignancyClinical trialsPatient outcomesPatient riskPrognostic biomarkerSurvival timeTherapeutic targetSuccessful drug targetsClinical decisionCancerSurvival dataTherapeutic developmentHuman cancersBiomarkersBiomarker analysisDriver genesCancer researchCancer driver genes
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
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