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Developing inhibitor combinations through identification of drug tolerant cell populations
Organization UNIVERSITY OF ILLINOIS AT CHICAGOLocation Chicago, UNITED STATESPosted 1 Apr 2024Deadline 31 Mar 2026 ⚠️
NIHUS FederalResearch GrantFY2025AddressAffectAssayBioassayBiologicalBiological AssayCancer PatientCancer TreatmentCancer cell lineCancersCell BodyCell Death InductionCell LineCell SurvivalCell ViabilityCellLineCellsCellular ExpansionCellular GrowthClinicClinicalClinical TrialsCombined Modality TherapyComputational toolkitDataData BasesDatabasesDisease stratificationDrug CombinationsDrug PrescribingDrug PrescriptionsDrug TargetingDrug ToleranceDrug usageDrugsEGF ReceptorEGFRERBB ProteinEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor KinaseEpidermal Growth Factor Receptor Protein-Tyrosine KinaseEpidermal Growth Factor-Urogastrone ReceptorsExhibitsExperimental ModelsExposure toExpression SignatureFluorescenceGene ExpressionGene Expression ProfileGene TranscriptionGeneralized GrowthGenetic TranscriptionGoalsGrowthHER1HeterogeneityHeterograftHeterologous TransplantationIn Situ HybridizationIndividualKnowledgeMalignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMapsMedicationMethodsModelingMultimodal TherapyMultimodal TreatmentNSCLCNSCLC - Non-Small Cell Lung CancerNon-Polyadenylated RNANon-Small Cell Lung CancerNon-Small-Cell Lung CarcinomaOncogene ProductsOncogene ProteinsOncologistOncoproteinsPathway interactionsPatientsPharmaceutical PreparationsPhenotypePopulationProcessRNARNA ExpressionRNA Gene ProductsRNA SeqRNA sequencingRNAseqRefractoryResearchResistanceRibonucleic AcidRouteSafetyStrains Cell LinesTGF-alpha ReceptorTestingTherapeuticTissue GrowthTranscriptionTransforming Growth Factor alpha ReceptorUrogastrone ReceptorValidationXenograftXenograft procedureXenotransplantationacquired drug resistanceanti-cancer therapybiologicc-erbB-1c-erbB-1 Proteincancer carecancer cellcancer clinical trialcancer therapycancer-directed therapycell growthchemotherapyclinical relevanceclinically relevantcohortcombination therapycombined modality treatmentcombined treatmentcomputational pipelinescomputational toolboxcomputational toolscomputational toolsetcomputerized toolscultured cell linedata basedesigndesigningdrug repositioningdrug repurposingdrug response predictiondrug usedrug/agenterbB-1erbB-1 Proto-Oncogene ProteinerbBlgene expression patterngene expression signaturehigh dimensional dataimprovedin silicoin situ Hybridization Geneticsin situ Hybridization Staining Methodin vivoindividual patientinhibitorinnovateinnovationinnovativeinsightlung cancer cellmalignancymedication prescriptionmulti-modal therapymulti-modal treatmentmultidimensional datamultidimensional datasetsmutantneoplasm/cancernew approachesnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnon-geneticnongeneticnovel approachesnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel strategiesnovel strategynovel therapeuticsnovel therapyoncology clinical trialontogenypathwaypatient stratificationpre-clinicalpreclinicalpredictive biological markerpredictive biomarkerspredictive markerpredictive molecular biomarkerprescribed medicationpreventpreventingproto-oncogene protein c-erbB-1repurposing agentrepurposing medicationresistance to therapyresistantresistant to therapyresponsescRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle moleculesingle-cell RNA sequencingsmall molecular inhibitorsmall moleculesmall molecule inhibitorstandard of carestratified patientsuccesstargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic agent developmenttherapeutic developmenttherapeutic resistancetherapy resistanttranscriptional profiletranscriptional signaturetranscriptome sequencingtranscriptomic sequencingtreatment resistancetumortumor xenograftvalidationsxeno-transplantxeno-transplantation
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PROJECT SUMMARY/ABSTRACT
Drug tolerant cells limit clinical success of many types of anticancer therapies. Drug tolerance has largely been
associated with cell heterogeneity. Surprisingly, identifying successful drug combinations has rarely been
done at the cell population level. We propose that the limited success of therapeutic strategies is due…
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