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
2013
A Transcriptional and Metabolic Signature of Primary Aneuploidy Is Present in Chromosomally Unstable Cancer Cells and Informs Clinical Prognosis
Sheltzer J. A Transcriptional and Metabolic Signature of Primary Aneuploidy Is Present in Chromosomally Unstable Cancer Cells and Informs Clinical Prognosis. Cancer Research 2013, 73: 6401-6412. PMID: 24041940, PMCID: PMC3901577, DOI: 10.1158/0008-5472.can-13-0749.Peer-Reviewed Original ResearchConceptsChromosomal instabilityPrimary cellsUnstable cancer cellsAneuploid cellsSubset of genesProliferation-independent mannerHigh mitotic activityCancer cell linesAggressive diseasePoor prognosisClinical prognosisTypes of aneuploidyPrimary aneuploidyCellular stressAbnormal karyotypeTranscriptional alterationsHuman patientsTCA cycle fluxCancerMetabolic signaturesAneuploid cancersTranscriptional signatureCancer cellsCancer linesMitotic activity