2024
Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation
Trogdon M, Abbott K, Arang N, Lande K, Kaur N, Tong M, Bakhoum M, Gutkind J, Stites E. Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation. Npj Systems Biology And Applications 2024, 10: 75. PMID: 39013872, PMCID: PMC11252164, DOI: 10.1038/s41540-024-00400-1.Peer-Reviewed Original ResearchConceptsSignaling networksMathematical models of biochemical reaction networksModels of biochemical reaction networksG-proteinCell signaling networksDisease-causing mutationsComputational systems biologyBiochemical reaction networksDownstream pathway activationSignaling phenotypeSystems biologyBioinformatics analysisGPCR signalingMutationsCo-occurring mutationsOncogenic mutationsPathway activationDiscovery toolPathwayReaction networkSignalCYSLTR2 mutationsDiscoveryPhenotypeMutually-exclusiveThe Abundance of KRAS and RAS Gene Mutations in Cancer
Stites E. The Abundance of KRAS and RAS Gene Mutations in Cancer. Methods In Molecular Biology 2024, 2797: 13-22. PMID: 38570449, DOI: 10.1007/978-1-0716-3822-4_2.Peer-Reviewed Original Research
2022
Therapeutic Targeting of RAS Mutant Cancers
Stites E, Paskvan K, Kato S. Therapeutic Targeting of RAS Mutant Cancers. 2022 DOI: 10.1017/9781009064828.Peer-Reviewed Original Research
2021
Identification of RAS mutant biomarkers for EGFR inhibitor sensitivity using a systems biochemical approach
McFall T, Stites E. Identification of RAS mutant biomarkers for EGFR inhibitor sensitivity using a systems biochemical approach. Cell Reports 2021, 37: 110096. PMID: 34910921, PMCID: PMC8867612, DOI: 10.1016/j.celrep.2021.110096.Peer-Reviewed Original ResearchConceptsSensitivity to EGFR inhibitionSubsets of mutationsRAS mutationsKRAS G13DCancer cell biologyEGFR inhibitionEpidermal growth factor receptor (EGFR)-targeted therapyTumor suppressor neurofibrominGene-basedBiophysical biomarkersInhibitor sensitivityCell biologyMutationsPersonalized medicineBiomarker strategiesKRAS mutantRasCancer treatmentKRASNF1BiomarkersBiophysical characteristicsG13DMutantsInhibitionCancer gene mutation frequencies for the U.S. population
Mendiratta G, Ke E, Aziz M, Liarakos D, Tong M, Stites E. Cancer gene mutation frequencies for the U.S. population. Nature Communications 2021, 12: 5961. PMID: 34645806, PMCID: PMC8514428, DOI: 10.1038/s41467-021-26213-y.Peer-Reviewed Original ResearchMeSH KeywordsComputational BiologyDNA-Binding ProteinsEpigenesis, GeneticGene Expression Regulation, NeoplasticGenetics, PopulationHumansIncidenceMutation RateNeoplasm ProteinsNeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Terminology as TopicTranscription FactorsTumor Suppressor Protein p53United StatesConceptsMutated driver genesMutant formsCancer driversCancer geneticsCancer casesDriver genesGene mutation frequencyMutated genesU.S. populationEpigenetic dysregulationMutation frequencyDevelopment of cancerGenesPublic healthEpidemiological dataCancer typesTargetable vulnerabilitiesCancerKMT2CPopulationMutationsHealthGeneticsKMT2DMathematical Modeling to Study KRAS Mutant-Specific Responses to Pathway Inhibition
Stites E. Mathematical Modeling to Study KRAS Mutant-Specific Responses to Pathway Inhibition. Methods In Molecular Biology 2021, 2262: 311-321. PMID: 33977486, PMCID: PMC8639139, DOI: 10.1007/978-1-0716-1190-6_19.Peer-Reviewed Original ResearchConceptsRegulates Ras signalingMutant Ras proteinsKRAS G13D mutationRas proteinsRAS communityRas mutantsRas signalingRas pathwayBiochemical reactionsWild-typeRasMutationsPathway inhibitionG13D mutationDose-response experimentsMutantsKnowledge of reaction mechanismsInhibitionEGFR inhibitionKRAS mutationsProteinKRAS
2020
Discernment between candidate mechanisms for KRAS G13D colorectal cancer sensitivity to EGFR inhibitors
McFall T, Schomburg N, Rossman K, Stites E. Discernment between candidate mechanisms for KRAS G13D colorectal cancer sensitivity to EGFR inhibitors. Cell Communication And Signaling 2020, 18: 179. PMID: 33153459, PMCID: PMC7643456, DOI: 10.1186/s12964-020-00645-3.Peer-Reviewed Original ResearchConceptsKRAS mutationsKRAS G13DEGFR inhibitorsColorectal cancerSensitivity to EGFR inhibitorsRas-GTP levelsSensitivity to cetuximabClinical trial evidenceWild-type RasGTPase activityKRAS G13D mutationBind NF1Tumor suppressor NF1EGFR inhibitionG13D mutationKRASCetuximabBiophysical studiesTrial evidenceG13DWild-typeNF1MutationsCellular modelEGFRAbstract 5509: Breaking the paradox breakers - RAF inhibitor mechanisms
Mendiratta G, McFall T, Stites E. Abstract 5509: Breaking the paradox breakers - RAF inhibitor mechanisms. Cancer Research 2020, 80: 5509-5509. DOI: 10.1158/1538-7445.am2020-5509.Peer-Reviewed Original ResearchSW48 colon cancer cellsMechanism of PAColon cancer cellsParadoxical activationRaf activationAmerican Association for Cancer ResearchATP-competitive inhibitorsDimer stabilityDownstream signalingUpstream mutationsOnco-proteinRafInhibitor mechanismCancer cellsV600 mutationMutationsRegulatory processesDriver mutationsMelanoma cellsSide effectsCombined treatmentPotential PAProteinDrug bindingNo PAA mechanism for the response of KRASG13D expressing colorectal cancers to EGFR inhibitors
McFall T, Stites E. A mechanism for the response of KRASG13D expressing colorectal cancers to EGFR inhibitors. Molecular & Cellular Oncology 2020, 7: 1701914. PMID: 32158916, PMCID: PMC7051129, DOI: 10.1080/23723556.2019.1701914.Peer-Reviewed Original ResearchEpidermal growth factor receptorKRAS mutationsColorectal cancer patients treated with cetuximabPhase 3 clinical trial dataResistance to epidermal growth factor receptorPatients treated with cetuximabCancer personalized medicineColorectal cancer patientsGrowth factor receptorFactor receptorCancer patientsKRASCancer cellsAspartic acid mutationAmino acid 13NRAS signalingTrial dataPatientsCetuximabPersonalized medicineTumor suppressorMutationsImpaired bindingAcid mutationsExperimental biology
2018
Quantitative Systems Pharmacology Analysis of KRAS G12C Covalent Inhibitors
Stites E, Shaw A. Quantitative Systems Pharmacology Analysis of KRAS G12C Covalent Inhibitors. CPT Pharmacometrics & Systems Pharmacology 2018, 7: 342-351. PMID: 29484842, PMCID: PMC5980551, DOI: 10.1002/psp4.12291.Peer-Reviewed Original ResearchConceptsRegulates Ras activitySystems biology approachBiology approachRas activationProtein turnoverKRAS-G12C covalent inhibitorsKRAS G12C inhibitorsSystems pharmacology analysisRasKRAS mutantDrug developmentG12C inhibitorsCovalent inhibitorsInhibitorsKRASMutantsPharmacological analysisMutationsKRAS G12C
2015
Cooperation between Noncanonical Ras Network Mutations
Stites E, Trampont P, Haney L, Walk S, Ravichandran K. Cooperation between Noncanonical Ras Network Mutations. Cell Reports 2015, 10: 307-316. PMID: 25600866, PMCID: PMC4503519, DOI: 10.1016/j.celrep.2014.12.035.Peer-Reviewed Original ResearchCollection of mutationsRAS pathway mutationsRas signaling networkGenomic data setsPathway mutationsTumor suppressor gene NF1Combinations of mutationsRandom mutagenesisRas mutantsNetwork genesSignaling networksGene NF1Genomic instabilityCancer phenotypeNF1 mutationsMutationsPromote cancerRasMutated cancersIncreased co-occurrenceMutantsMutagenesisGenesPhenotypeNF1
2014
Abstract PR04: Cooperation between Ras network mutations in cancer
Stites E, Trampont P, Haney L, Walk S, Ravichandran K. Abstract PR04: Cooperation between Ras network mutations in cancer. Molecular Cancer Research 2014, 12: pr04-pr04. DOI: 10.1158/1557-3125.rasonc14-pr04.Peer-Reviewed Original ResearchRas signaling networkSignaling networksGenomic dataRAS pathway mutationsRas mutantsNetwork mutationGenomic data setsCancer Cell Line EncyclopediaCancer genome sequencingPathway mutationsTumor suppressor gene NF1Wild-type cellsCancer genomic dataGenome sequenceTumor suppressor gene mutationsCancer Genome AtlasGene NF1Cell-based experimentsDisplay synergyMutational pathwaysRAS networkRas oncogeneCo-occurrenceMutationsRas
2013
Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine
Stites E. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine. Physical Biology 2013, 10: 026004. PMID: 23406820, DOI: 10.1088/1478-3975/10/2/026004.Peer-Reviewed Original ResearchConceptsBiochemical networksCancer biologyInvestigate cancer biologyDisrupt cellular processesAcquisition of mutationsCellular processesClinical management of cancer patientsMutated genesCancer medicineMolecular biologyExperimental biologyFeatures of cancerBiologyMutationsMechanistic modelExperimental approachGenesMolecular reactionsPace of progressKinetic mechanistic modelsCancerManagement of cancer patients
2011
Mechanistic modeling to investigate signaling by oncogenic Ras mutants
Stites E, Ravichandran K. Mechanistic modeling to investigate signaling by oncogenic Ras mutants. WIREs Mechanisms Of Disease 2011, 4: 117-127. PMID: 21766467, DOI: 10.1002/wsbm.156.Peer-Reviewed Original ResearchConceptsCell signaling networksSignaling networksCancer phenotypeMutant Ras signalingAcquisition of mutationsRas signalingCell signalingBiochemistry of proteinsLevel of signalMutated genesExpression levelsBiochemical reaction mechanismsPhenotypeMechanistic modelInvestigated signalSignalGenesMutationsRasProteinCancerIndividual reactionsExpression