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-exclusiveCancer research is not correlated with driver gene mutation burdens
Mendiratta G, Liarakos D, Tong M, Ito S, Ke E, Goshua G, Stites E. Cancer research is not correlated with driver gene mutation burdens. Med 2024, 5: 832-838.e4. PMID: 38908369, DOI: 10.1016/j.medj.2024.05.013.Peer-Reviewed Original ResearchCancer patient populationCancer researchCancer research effortsResearch allocation decisionsNational InstitutePatient populationResearch fundingBurdenBurden of mutationsFunding decisionsCancerGenetic driversGene mutation burdenFunding amountFundingGenetic drivers of cancerAllocation decisionsCancer-associated genesEpidemiologyDrivers of cancerMutational burdenBaselineEffortsFactorsBalance of prioritiesThe 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 ResearchDecreasing alloimmunization‐specific mortality in sickle cell disease in the United States: Cost‐effectiveness of a shared transfusion resource
Ito S, Pandya A, Hauser R, Krishnamurti L, Stites E, Tormey C, Krumholz H, Hendrickson J, Goshua G. Decreasing alloimmunization‐specific mortality in sickle cell disease in the United States: Cost‐effectiveness of a shared transfusion resource. American Journal Of Hematology 2024, 99: 570-576. PMID: 38279581, DOI: 10.1002/ajh.27211.Peer-Reviewed Original ResearchSickle cell diseaseDelayed hemolytic transfusion reactionQuality-adjusted life expectancyAlloimmunized patientsPatient populationRed blood cell alloimmunizationCell diseaseCost-effective interventionMedical expenditure of patientsHealth system perspectiveExpenditure of patientsIncremental cost-effectiveness ratioHemolytic transfusion reactionsUnited StatesMarkov cohort simulationCost-effectiveAverage patient populationCost-effectiveness ratioBirth cohortAnalytical time horizonAntibody historyCohort simulationTransfusionTransfusion reactionsLife expectancy
2023
Theoretical analysis reveals a role for RAF conformational autoinhibition in paradoxical activation
Mendiratta G, Stites E. Theoretical analysis reveals a role for RAF conformational autoinhibition in paradoxical activation. ELife 2023, 12: e82739. PMID: 37823369, PMCID: PMC10627510, DOI: 10.7554/elife.82739.Peer-Reviewed Original ResearchMaking inroads to precision medicine for the treatment of autoimmune diseases: Harnessing genomic studies to better diagnose and treat complex disorders
Baglaenko Y, Wagner C, Bhoj V, Brodin P, Gershwin M, Graham D, Invernizzi P, Kidd K, Korsunsky I, Levy M, Mammen A, Nizet V, Ramirez-Valle F, Stites E, Williams M, Wilson M, Rose N, Ladd V, Sirota M. Making inroads to precision medicine for the treatment of autoimmune diseases: Harnessing genomic studies to better diagnose and treat complex disorders. Cambridge Prisms Precision Medicine 2023, 1: e25. PMID: 38550937, PMCID: PMC10953750, DOI: 10.1017/pcm.2023.14.Peer-Reviewed Original ResearchAutoimmune diseasesPrecision medicinePathogenic autoantigenPatient subtypesDisease heterogeneityComplex etiologyMolecular profilingDiseaseAccount individual variabilityDisease mechanismsForeign cellsMolecular pathwaysNatural defense systemComplex disorderDisease treatmentHealthy tissueIndividual variabilityOwn cellsTreatmentMedicineTherapeuticsDefense systemCurrent understandingCellsAutoantigensComputational Random Mutagenesis to Investigate RAS Mutant Signaling
Stites E. Computational Random Mutagenesis to Investigate RAS Mutant Signaling. Methods In Molecular Biology 2023, 2634: 329-335. PMID: 37074586, PMCID: PMC10530643, DOI: 10.1007/978-1-0716-3008-2_15.Peer-Reviewed Original Research
2022
Co-targeting KRAS G12C and EGFR reduces both mutant and wild-type RAS-GTP
McFall T, Trogdon M, Guizar A, Langenheim J, Sisk-Hackworth L, Stites E. Co-targeting KRAS G12C and EGFR reduces both mutant and wild-type RAS-GTP. Npj Precision Oncology 2022, 6: 86. PMID: 36418474, PMCID: PMC9684405, DOI: 10.1038/s41698-022-00329-w.Peer-Reviewed Original ResearchTherapeutic 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 ResearchHow often is each gene mutated within the cancer patient population?
Mendiratta G, Jones M, Stites E. How often is each gene mutated within the cancer patient population? Molecular & Cellular Oncology 2022, 9: 2065176. PMID: 35529901, PMCID: PMC9067461, DOI: 10.1080/23723556.2022.2065176.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 mutationsProteinKRASKRAS‐Mutated, Estrogen Receptor‐Positive Low‐Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery
Kato S, McFall T, Takahashi K, Bamel K, Ikeda S, Eskander R, Plaxe S, Parker B, Stites E, Kurzrock R. KRAS‐Mutated, Estrogen Receptor‐Positive Low‐Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery. The Oncologist 2021, 26: e530-e536. PMID: 33528846, PMCID: PMC8018312, DOI: 10.1002/onco.13702.Peer-Reviewed Original ResearchConceptsMEK inhibitorsMechanism of actionOvarian cancerAromatase inhibitorsEstrogen modulationKRAS-mutantLow-grade serous ovarian cancerCombination of trametinibEstrogen receptor-positiveSerous ovarian cancerPrecision medicine strategiesPI3K inhibitorsReceptor-positiveCombination therapyEstrogen depletionTamoxifenTrametinibAgonist effectsIn vitro investigationLetrozoleEstrogenIn vitro experimentsMedicine strategiesMEKExceptional response
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 modelEGFRReal-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy
Kato S, Kim K, Lim H, Boichard A, Nikanjam M, Weihe E, Kuo D, Eskander R, Goodman A, Galanina N, Fanta P, Schwab R, Shatsky R, Plaxe S, Sharabi A, Stites E, Adashek J, Okamura R, Lee S, Lippman S, Sicklick J, Kurzrock R. Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy. Nature Communications 2020, 11: 4965. PMID: 33009371, PMCID: PMC7532150, DOI: 10.1038/s41467-020-18613-3.Peer-Reviewed Original ResearchConceptsMolecular tumor boardOverall survivalTumor boardNext-generation sequencingReviewed patient characteristicsResistant to monotherapyProgression-freeOncological outcomesRemission rateChoice regimenGenomic alterationsPatient characteristicsRecommended drugsMolecular findingsPatientsTherapyMaster protocolCancer targetPhysician-directedPFSPrecision strategySurvivalDrugMedication accessOutcomesThe Interpretation of SARS-CoV-2 Diagnostic Tests
Stites EC, Wilen CB. The Interpretation of SARS-CoV-2 Diagnostic Tests. Med 2020, 1: 78-89. PMID: 32864639, PMCID: PMC7441939, DOI: 10.1016/j.medj.2020.08.001.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 diagnostic testsCOVID-19SARS-CoV-2Diagnostic laboratory testingAsymptomatic individualsOngoing COVID-19 pandemicGeneral populationTesting utilizationMedical careDiagnostic testsMedical communityInformed decision makingCOVID-19 pandemicImmunity passportsTest interpretationDiseaseLaboratory testingAbstract 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 PAAbstract 37: Computational analysis of the KRAS G13D colorectal cancer response to EGFR inhibition with an alternatively parameterized model
McFall T, Stites E. Abstract 37: Computational analysis of the KRAS G13D colorectal cancer response to EGFR inhibition with an alternatively parameterized model. Clinical Cancer Research 2020, 26: 37-37. DOI: 10.1158/1557-3265.advprecmed20-37.Peer-Reviewed Original ResearchColon cancer cellsMultiple colon cancer cell linesBiochemical rate constantsCancer cellsColon cancer cell linesCell linesResponse to EGFR inhibitionKRAS mutantRAS biologyCancer cell linesRas signalingEGFR inhibitionMedicinal drug developmentSignaling regulationComputational analysisPersonalized cancer medicineMutantsG13D mutantWild-typeCombination of computational modelingEGFR inhibitor cetuximabColorectal cancer patientsDrug developmentCellsCancer medicineA Biophysical Basis for a Targeted Therapy Exceptional Responder KRAS Mutation
Stites E, McFall T. A Biophysical Basis for a Targeted Therapy Exceptional Responder KRAS Mutation. Biophysical Journal 2020, 118: 451a. DOI: 10.1016/j.bpj.2019.11.2515.Peer-Reviewed Original Research