2024
662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors
Mitchell S, Khan B, Payumo F, Gabriela Chiorean E, Gahvari Z, Randolph Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Schoenfeld A, Punekar S, Zhao D, Basu S, Nagorsen D. 662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors. 2024, a759-a759. DOI: 10.1136/jitc-2024-sitc2024.0662.Peer-Reviewed Original ResearchThe 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 ResearchTopical trametinib for epidermal and sebaceous nevi in a child with Schimmelpenning‐Feuerstein‐Mims syndrome
Haller C, Leszczynska M, Brichta L, Maier E, Riddington I, Choate K, Levy M. Topical trametinib for epidermal and sebaceous nevi in a child with Schimmelpenning‐Feuerstein‐Mims syndrome. Pediatric Dermatology 2024, 41: 523-525. PMID: 38273779, PMCID: PMC11096062, DOI: 10.1111/pde.15523.Peer-Reviewed Original Research
2023
The Evolving Role for Systemic Therapy in Resectable Non-small Cell Lung Cancer
Grant M, Woodard G, Goldberg S. The Evolving Role for Systemic Therapy in Resectable Non-small Cell Lung Cancer. Hematology/Oncology Clinics Of North America 2023, 37: 513-531. PMID: 37024389, DOI: 10.1016/j.hoc.2023.02.003.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerMetastatic non-small cell lung cancerResectable non-small cell lung cancerImmuno-oncology agentsHistologic classification systemUnited States FoodResectable tumorsSystemic therapyDriver alterationsDrug AdministrationStates FoodSystemic managementPatientsTherapyCancerEvolving roleClassification systemNTRKHER2TumorsKRASEGFRBRAF
2022
RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma
East P, Kelly G, Biswas D, Marani M, Hancock D, Creasy T, Sachsenmeier K, Swanton C, Downward J, de Carné Trécesson S. RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma. Nature Communications 2022, 13: 5632. PMID: 36163168, PMCID: PMC9512813, DOI: 10.1038/s41467-022-33290-0.Peer-Reviewed Original ResearchConceptsResponse to chemotherapyLung adenocarcinomaRas oncogene activationOncogenic activityKRAS wild-type tumorsReduced response to chemotherapyWild-type tumorsKRAS mutant tumorsResistance to therapyCohort of patientsAdverse clinical outcomesResponse to treatmentRAS pathway activationActive patient groupAggressive diseaseMutant tumorsKRAS mutationsClinical outcomesPreclinical studiesActivating mutationsClinical decision-makingGenetic alterationsPatient stratificationPatient groupKRASTherapeutic 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 characteristicsG13DMutantsInhibitionA mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma
Fitzgerald B, Connolly KA, Cui C, Fagerberg E, Mariuzza DL, Hornick NI, Foster GG, William I, Cheung JF, Joshi NS. A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma. Cell Reports Methods 2021, 1: 100080. PMID: 34632444, PMCID: PMC8500377, DOI: 10.1016/j.crmeth.2021.100080.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaNeoantigen expressionTumor-specific CD8 T cellsCD8 T cellsImmune checkpoint therapyInfection-induced inflammationExpression of neoantigensCommon lung cancerLUAD cell linesCheckpoint therapyLung cancerTherapeutic responseT cellsImmune responseMouse modelCell responsesTumor inductionTumorsAdenocarcinomaCell linesNeoantigensKRASFuture studiesExpressionImmunotherapyMathematical 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 modelEGFRKRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities
Luchini C, Paolino G, Mattiolo P, Piredda M, Cavaliere A, Gaule M, Melisi D, Salvia R, Malleo G, Shin J, Cargnin S, Terrazzino S, Lawlor R, Milella M, Scarpa A. KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities. Journal Of Experimental & Clinical Cancer Research 2020, 39: 227. PMID: 33115526, PMCID: PMC7594413, DOI: 10.1186/s13046-020-01732-6.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaAnti-PD-1/PD-L1 agentsDefective DNA mismatch repairComprehensive molecular profilingMicrosatellite instabilityKinase fusion geneDetermination of KRASTherapeutic molecular targetsHistological diagnosisKRAS mutationsBRAF mutationsDuctal adenocarcinomaKinase inhibitorsTailored treatmentTumorMAPK inhibitorFusion geneGenetic landscapeMolecular targetsKRASDeadly diseaseDNA mismatch repairMolecular traitsSyndecan-1 and KRAS Gene Expression Signature Associates With Patient Survival in Pancreatic Cancer.
Wu Y, Huang H, Fervers B, Lu L. Syndecan-1 and KRAS Gene Expression Signature Associates With Patient Survival in Pancreatic Cancer. Pancreas 2020, 49: 1187-1194. PMID: 32898003, DOI: 10.1097/mpa.0000000000001654.Peer-Reviewed Original ResearchConceptsSyndecan-1Patient survivalPancreatic cancerAdjusted hazard ratioPancreatic cancer patientsKRAS somatic mutationsSDC1 mRNASomatic mutationsHazard ratioCancer patientsClinical dataSurvival analysisKRASPatientsKyoto EncyclopediaKRAS mRNAElevated mortalityGenomes (KEGG) pathway analysisCancerPathway analysisLower methylationMolecular characteristicsSurvivalMRNANegative correlationThe mir181ab1 cluster promotes kras-driven oncogenesis and progression in lung and pancreas
Valencia K, Erice O, Kostyrko K, Hausmann S, Guruceaga E, Tathireddy A, Flores NM, Sayles LC, Lee AG, Fragoso R, Sun TQ, Vallejo A, Roman M, Entrialgo-Cadierno R, Migueliz I, Razquin N, Fortes P, Lecanda F, Lu J, Ponz-Sarvise M, Chen CZ, Mazur PK, Sweet-Cordero EA, Vicent S. The mir181ab1 cluster promotes kras-driven oncogenesis and progression in lung and pancreas. Journal Of Clinical Investigation 2020, 130: 1879-1895. PMID: 31874105, PMCID: PMC7108928, DOI: 10.1172/jci129012.Peer-Reviewed Original ResearchConceptsPotential therapeutic targetNew molecular targetsPancreatic cancerMouse modelTherapeutic targetHuman cancer cellsDownstream effector pathwaysKRASMolecular targetsCancerCancer cellsEffector pathwaysKey modulatorNonredundant roleLungProliferative advantageProgressionUnknown roleOncogenesisPhenotypePatientsTherapyPancreasMicroRNA clusterA 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
2019
A systems mechanism for KRAS mutant allele–specific responses to targeted therapy
McFall T, Diedrich J, Mengistu M, Littlechild S, Paskvan K, Sisk-Hackworth L, Moresco J, Shaw A, Stites E. A systems mechanism for KRAS mutant allele–specific responses to targeted therapy. Science Signaling 2019, 12 PMID: 31551296, PMCID: PMC6864030, DOI: 10.1126/scisignal.aaw8288.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorWild-type Ras activationColorectal cancerSensitivity to EGFR inhibitionEpidermal growth factor receptor inhibitionKRAS mutantEGFR-independent mannerAllele-specific responsesRas activationGrowth factor receptorTumor suppressor neurofibrominPatient tumorsAntibody cetuximabTargeted therapyMechanisms of EGFR signalingCRC patientsEGFR inhibitionCancer treatment decisionsRas mutationsFactor receptorKRASTherapeutic strategiesTreatment decisionsEGFR SignalingPatients
2018
Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS
Kitajima S, Asahina H, Chen T, Guo S, Quiceno L, Cavanaugh J, Merlino A, Tange S, Terai H, Kim J, Wang X, Zhou S, Xu M, Wang S, Zhu Z, Thai T, Takahashi C, Wang Y, Neve R, Stinson S, Tamayo P, Watanabe H, Kirschmeier P, Wong K, Barbie D. Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS. Cancer Cell 2018, 34: 439-452.e6. PMID: 30205046, PMCID: PMC6422029, DOI: 10.1016/j.ccell.2018.08.009.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsAntineoplastic Agents, ImmunologicalCarcinoma, Non-Small-Cell LungCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmHEK293 CellsHumansImmunity, InnateInsulin-Like Growth Factor ILung NeoplasmsMiceMice, TransgenicMitogen-Activated Protein Kinase KinasesPhosphoproteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Transcription FactorsYAP-Signaling ProteinsConceptsGenetically engineered mouse modelsMediators of acquired resistanceDownstream of KRASBET inhibitor JQ1Effective therapeutic strategyTumor shrinkageTargeted therapyIntermittent treatmentYAP1 signalingMouse modelPathway inhibitionBET inhibitionTherapeutic strategiesInhibitor JQ1YAP1 upregulationOncogenic KrasBET inhibitorsOvercome resistancePromoter acetylationIntrinsic resistancePotential translationKRASMEKInnateInhibitionComparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing
Kim AS, Bartley AN, Bridge JA, Kamel-Reid S, Lazar AJ, Lindeman NI, Long TA, Merker JD, J. AJ, Rimm DL, Rothberg PG, Vasalos P, Moncur JT. Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing. JAMA Oncology 2018, 4: 838-841. PMID: 29242895, PMCID: PMC6145687, DOI: 10.1001/jamaoncol.2017.4021.Peer-Reviewed Original ResearchConceptsLaboratory-developed testsPT responseCompanion diagnosticsClinical laboratory testingKRAS testingOncology CommitteeMAIN OUTCOMEUS FoodDrug AdministrationPractice characteristicsDiagnostic testingTumor contentProficiency testingVariant-specific differencesEGFRBRAFClinical diagnostic testingMajority of laboratoriesKRASAssaysLaboratory testingPerformance of laboratoriesKit manufacturersResponseParticipantsQuantitative 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 G12CHeterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C
Cannataro VL, Gaffney SG, Stender C, Zhao ZM, Philips M, Greenstein AE, Townsend JP. Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C. Oncogene 2018, 37: 2444-2455. PMID: 29453361, DOI: 10.1038/s41388-017-0105-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SubstitutionAnimalsCase-Control StudiesDisease ProgressionDrug Resistance, NeoplasmFemaleGenetic HeterogeneityHigh-Throughput Nucleotide SequencingHumansMaleMiceMice, Inbred BALB CMice, NudeNeoplasmsOncogenesPoint MutationPolymorphism, Single NucleotideProto-Oncogene Proteins p21(ras)Sequence Analysis, DNAYoung AdultConceptsTime of treatmentTargeted therapyLung tumorsDe novo mutationsNew targeted therapiesPatient-derived xenograftsHighest fitness advantageKRAS G12C variantNovo mutationsEvidence of heterogeneityNovel KRAS mutationPreclinical promiseSuch therapyHigh prevalenceKRAS mutationsTreatment resistanceBRAF V600EKRASTherapyTargeted inhibitorsTumorsAssociated oncogeneRAS genesHuman cancersOncogenic mutationsAdaptive and Reversible Resistance to Kras Inhibition in Pancreatic Cancer Cells
Chen PY, Muzumdar M, Dorans KJ, Robbins R, Bhutkar A, Del Rosario A, Mertins P, Qiao J, Schafer AC, Gertler F, Carr S, Jacks T. Adaptive and Reversible Resistance to Kras Inhibition in Pancreatic Cancer Cells. Cancer Research 2018, 78: 985-1002. PMID: 29279356, PMCID: PMC5837062, DOI: 10.1158/0008-5472.can-17-2129.Peer-Reviewed Original ResearchConceptsMurine PDAC cellsPDAC cellsNontranscriptional mechanismsKRAS inhibitorsGlobal phosphoproteomic profilingActivated KRASHallmark genetic alterationsTranscriptional changesPhosphoproteomic profilingCell signalingCell statesPathway componentsTumor-initiating capacityPancreatic ductal adenocarcinomaTemporal controlGenetic alterationsCell morphologyMechanistic directionsKras expressionKRASCellsProliferative kineticsInhibitorsNovel KRAS inhibitorsAdherence properties
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