2020
Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial
Goldberg SB, Schalper KA, Gettinger SN, Mahajan A, Herbst RS, Chiang AC, Lilenbaum R, Wilson FH, Omay SB, Yu JB, Jilaveanu L, Tran T, Pavlik K, Rowen E, Gerrish H, Komlo A, Gupta R, Wyatt H, Ribeiro M, Kluger Y, Zhou G, Wei W, Chiang VL, Kluger HM. Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2020, 21: 655-663. PMID: 32251621, PMCID: PMC7380514, DOI: 10.1016/s1470-2045(20)30111-x.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, TumorBrain NeoplasmsCarcinoma, Non-Small-Cell LungFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm MetastasisConceptsBrain metastasis responseYale Cancer CenterPD-L1 expressionPhase 2 trialUntreated brain metastasesBrain metastasesAdrenal insufficiencyAdverse eventsMetastasis responseCNS diseaseCancer CenterCohort 2Cohort 1Eastern Cooperative Oncology Group performance statusTreatment-related serious adverse eventsModified Response Evaluation CriteriaStage IV NSCLCTreatment-related deathsAcute kidney injuryPD-1 blockadeSerious adverse eventsSolid Tumors criteriaPhase 2 studyProportion of patientsResponse Evaluation Criteria
2018
Amplification of Wild-type KRAS Imparts Resistance to Crizotinib in MET Exon 14 Mutant Non–Small Cell Lung Cancer
Bahcall M, Awad MM, Sholl LM, Wilson FH, Xu M, Wang S, Palakurthi S, Choi J, Ivanova E, Leonardi GC, Ulrich BC, Paweletz CP, Kirschmeier PT, Watanabe M, Baba H, Nishino M, Nagy RJ, Lanman RB, Capelletti M, Chambers ES, Redig AJ, VanderLaan PA, Costa DB, Imamura Y, Jänne P. Amplification of Wild-type KRAS Imparts Resistance to Crizotinib in MET Exon 14 Mutant Non–Small Cell Lung Cancer. Clinical Cancer Research 2018, 24: 5963-5976. PMID: 30072474, PMCID: PMC6279568, DOI: 10.1158/1078-0432.ccr-18-0876.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell Line, TumorCrizotinibDisease Models, AnimalDNA Copy Number VariationsDrug Resistance, NeoplasmExonsGene AmplificationGene Expression Regulation, NeoplasticHumansIn Situ Hybridization, FluorescenceLung NeoplasmsMiceModels, BiologicalMutationPhosphatidylinositol 3-KinasesPositron Emission Tomography Computed TomographyProtein Kinase InhibitorsProto-Oncogene Proteins c-metProto-Oncogene Proteins p21(ras)Signal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerMutant non-small cell lung cancerCell lung cancerPatient-derived cell linesCrizotinib resistanceLung cancerCell linesLong-term efficacyPI3KEGFR ligandsPI3K inhibitionCombination therapyEffective therapyMET inhibitorsSuperior efficacyPatient tumorsDrug combinationsMET inhibitionTherapeutic strategiesParental cell lineMEK inhibitionDrug resistanceRecurrent genetic eventsK inhibitionCompensatory induction
2014
Genetic modifiers of EGFR dependence in non-small cell lung cancer
Sharifnia T, Rusu V, Piccioni F, Bagul M, Imielinski M, Cherniack AD, Pedamallu CS, Wong B, Wilson FH, Garraway LA, Altshuler D, Golub TR, Root DE, Subramanian A, Meyerson M. Genetic modifiers of EGFR dependence in non-small cell lung cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 18661-18666. PMID: 25512530, PMCID: PMC4284598, DOI: 10.1073/pnas.1412228112.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungCell Line, TumorErbB ReceptorsGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansLung NeoplasmsMAP Kinase Signaling SystemMembrane GlycoproteinsProtein-Tyrosine KinasesProto-Oncogene Proteins c-mosProto-Oncogene Proteins c-rafReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2Receptor, trkAReceptor, trkBConceptsEpidermal growth factor receptorEGFR dependenceMEK-ERKUnbiased gene expression profilingGenetic modifiersEGFR-independent activationKinase-related genesGene expression profilingEGFR-mutant NSCLC cellsGrowth factor receptorGenetic basisKinase geneEGFR activityGenesPI3K-AktAkt pathwayPC9 cellsPI3K-mTORFactor receptorKinaseNSCLC cellsKinase inhibitorsCombined inhibitionMutationsCells