2022
RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition.
Hunihan L, Zhao D, Lazowski H, Li M, Qian Y, Abriola L, Surovtseva YV, Muthusamy V, Tanoue LT, Rothberg BE, Schalper KA, Herbst RS, Wilson FH. RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition. Clinical Cancer Research 2022, 28: 3091-3103. PMID: 35247929, PMCID: PMC9288503, DOI: 10.1158/1078-0432.ccr-21-4291.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungCarcinogenesisHumansLung NeoplasmsMitogen-Activated Protein Kinase KinasesRas-GRF1ConceptsLung adenocarcinomaSmoking historyPack-year smoking historyMinimal smoking historySubset of patientsPancreatic ductal adenocarcinoma cell linesPotential treatment strategyTight junction protein occludinJunction protein occludinWhole-exome sequencingAdenocarcinoma cell lineAdvanced malignanciesCancer Genome AtlasRaf-MEKAdvanced tumorsMultiple malignanciesTreatment strategiesKRAS mutationsTherapeutic strategiesTherapeutic targetOncogenic RAS SignalingRelated commentaryOncogenic driversMEK inhibitionOncogenic alterations
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
2017
Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study
Ghazani AA, Oliver NM, St. Pierre JP, Garofalo A, Rainville IR, Hiller E, Treacy DJ, Rojas-Rudilla V, Wood S, Bair E, Parello M, Huang F, Giannakis M, Wilson FH, Stover EH, Corsello SM, Nguyen T, Rana HQ, Church AJ, Lowenstein C, Cibulskis C, Amin-Mansour A, Heng J, Brais L, Santos A, Bauer P, Waldron A, Lo P, Gorman M, Lydon CA, Welch M, McNamara P, Gabriel S, Sholl LM, Lindeman NI, Garber JE, Joffe S, Van Allen EM, Gray SW, Jänne P, Garraway LA, Wagle N. Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study. Genetics In Medicine 2017, 19: 787-795. PMID: 28125075, DOI: 10.1038/gim.2016.191.Peer-Reviewed Original ResearchConceptsClinical evidenceCancer precision medicineWhole-exome sequencing dataPrecision medicineMolecular tumor boardTumor biopsy samplesGerm-line alterationsGerm-line variantsProtocol-based approachPrecision medicine studiesMetastatic colorectalPatient preferencesTumor boardLung adenocarcinomaClinical careBlood samplesBiopsy samplesClinical relevanceClinical teamClinical meaningTherapeutic relevanceUnknown significanceVariant reviewMedicine studiesGenomic alterations
2015
A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer
Wilson FH, Johannessen CM, Piccioni F, Tamayo P, Kim JW, Van Allen EM, Corsello SM, Capelletti M, Calles A, Butaney M, Sharifnia T, Gabriel SB, Mesirov JP, Hahn WC, Engelman JA, Meyerson M, Root DE, Jänne PA, Garraway LA. A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer. Cancer Cell 2015, 27: 397-408. PMID: 25759024, PMCID: PMC4398996, DOI: 10.1016/j.ccell.2015.02.005.Peer-Reviewed Original ResearchConceptsFunctional genetic studiesG protein-coupled receptorsResistance driversALK inhibitionFunctional landscapeGenetic studiesLung cancer cellsALK inhibitor resistanceResistance pathwaysMechanisms of resistanceReceptor familyPKC activationPurinergic receptor familyPKC inhibitionCrizotinib-resistant ALKCancer cellsInhibitor resistanceGene signatureDependent mechanismLung cancerLung tumorsALK inhibitorsInhibitionALKMechanism
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