2024
A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition
Lenchner D, Petrova Z, Hunihan L, Ashtekar K, Walther Z, Wilson F. A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition. Npj Precision Oncology 2024, 8: 3. PMID: 38182677, PMCID: PMC10770066, DOI: 10.1038/s41698-023-00490-w.Peer-Reviewed Original Research
2023
MA15.07 NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC
Gettinger S, Goldberg S, Chiang A, Wilson F, Kim S, Rowen E, Gerrish H, Duffield E, Davies M, Dest V, Jackson R, Pope J, Myint H, Langermann S, Cheng W, Rimm D, Chen L, Herbst R. MA15.07 NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC. Journal Of Thoracic Oncology 2023, 18: s155. DOI: 10.1016/j.jtho.2023.09.224.Peer-Reviewed Original Research
2022
Making National Cancer Institute–Designated Comprehensive Cancer Center Knowledge Accessible to Community Oncologists via an Online Tumor Board: Longitudinal Observational Study
Kalra M, Henry E, McCann K, Karuturi MS, Bustamante Alvarez JG, Parkes A, Wesolowski R, Wei M, Mougalian SS, Durm G, Qin A, Schonewolf C, Trivedi M, Armaghani AJ, Wilson FH, Iams WT, Turk AA, Vikas P, Cecchini M, Lubner S, Pathak P, Spencer K, Koshkin VS, Labriola MK, Marshall CH, Beckermann KE, , Sharifi MN, Bejjani AC, Hotchandani V, Housri S, Housri N. Making National Cancer Institute–Designated Comprehensive Cancer Center Knowledge Accessible to Community Oncologists via an Online Tumor Board: Longitudinal Observational Study. JMIR Cancer 2022, 8: e33859. PMID: 35588361, PMCID: PMC9164098, DOI: 10.2196/33859.Peer-Reviewed Original ResearchRASGRF1 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 ResearchConceptsLung 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
2021
Osimertinib in EGFR-Mutant Non-Small Cell Lung Carcinoma: Clinical Activity and Mechanisms of Resistance
Talsania A, Zhang J, Wilson F. Osimertinib in EGFR-Mutant Non-Small Cell Lung Carcinoma: Clinical Activity and Mechanisms of Resistance. Current Cancer Research 2021, 65-73. DOI: 10.1007/978-3-030-74028-3_4.ChaptersNon-small cell lung carcinomaEGFR-mutant non-small cell lung carcinomaEpidermal growth factor receptorCell lung carcinomaLung carcinomaSmall cell lung carcinomaEGFR-Mutant NonMajor therapeutic challengeCare of patientsPotential therapeutic strategyConstitutive EGFR activationThird-generation EGFR inhibitorsUpregulation of pathwaysGrowth factor receptorResistance mechanismsAdjuvant settingTherapeutic challengeMechanisms of resistanceClinical activityTherapeutic strategiesClinical developmentSmall molecule inhibitorsEGFR inhibitorsFactor receptorEGFR activation
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 ResearchConceptsBrain 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
2019
Larotrectinib in NTRK-Rearranged Solid Tumors
Wilson FH, Herbst RS. Larotrectinib in NTRK-Rearranged Solid Tumors. Biochemistry 2019, 58: 1555-1557. PMID: 30865435, PMCID: PMC7356829, DOI: 10.1021/acs.biochem.9b00126.Peer-Reviewed Original Research
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 inductionYale Cancer Center Precision Medicine Tumor Board: one tumour, multiple targets
Stewart T, Finberg K, Walther Z, Sklar JL, Hafez N, Eder JP, Anderson K, Wilson F, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: one tumour, multiple targets. The Lancet Oncology 2018, 19: 1567-1568. PMID: 32956641, DOI: 10.1016/s1470-2045(18)30759-9.Peer-Reviewed Case Reports and Technical NotesERBB Signaling Interrupted: Targeting Ligand-Induced Pathway Activation
Wilson FH, Politi K. ERBB Signaling Interrupted: Targeting Ligand-Induced Pathway Activation. Cancer Discovery 2018, 8: 676-678. PMID: 29858224, PMCID: PMC6330656, DOI: 10.1158/2159-8290.cd-18-0368.Commentaries, Editorials and Letters
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
2016
MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
Kryukov GV, Wilson FH, Ruth JR, Paulk J, Tsherniak A, Marlow SE, Vazquez F, Weir BA, Fitzgerald ME, Tanaka M, Bielski CM, Scott JM, Dennis C, Cowley GS, Boehm JS, Root DE, Golub TR, Clish CB, Bradner JE, Hahn WC, Garraway LA. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science 2016, 351: 1214-1218. PMID: 26912360, PMCID: PMC4997612, DOI: 10.1126/science.aad5214.Peer-Reviewed Original ResearchConceptsProtein arginine methyltransferase 5Methylthioadenosine phosphorylaseCancer cell linesMultiple cancer lineagesPutative drug targetsCell linesTumor suppressor geneComprehensive genomic profilingCancer cell dependenciesEnzyme methylthioadenosine phosphorylaseArginine methyltransferaseCancer lineagesFunctional characterizationCancer dependenciesPRMT5 inhibitorsSuppressor geneDrug targetsTherapeutic strategiesPreferential impairmentMTAP deletionEnzymatic activityGenomic alterationsGenomic profilingCell dependencyCancer cells
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
2012
Administration of Vincristine in a Patient with Machado-Joseph Disease
Colpo A, Wilson FH, Nardi V, Hochberg E. Administration of Vincristine in a Patient with Machado-Joseph Disease. Oncology 2012, 82: 165-167. PMID: 22433430, PMCID: PMC3701890, DOI: 10.1159/000336602.Peer-Reviewed Original ResearchConceptsMachado-Joseph diseaseChemotherapy-induced peripheral neurotoxicityDose-limiting side effectVinca alkaloidsSevere vincristine neurotoxicityAdministration of vincristinePeripheral neurotoxicitySpinocerebellar ataxia type 3Vincristine neurotoxicityNeurological symptomsAtaxia type 3Side effectsHereditary neuropathyAntineoplastic drugsType 3NeurotoxicityDiseaseSignificant numberNeuropathyExacerbationPatientsVincristineSymptomsAdministration
2010
Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells
Dutt S, Narla A, Lin K, Mullally A, Abayasekara N, Megerdichian C, Wilson FH, Currie T, Khanna-Gupta A, Berliner N, Kutok JL, Ebert BL. Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 2010, 117: 2567-2576. PMID: 21068437, PMCID: PMC3062351, DOI: 10.1182/blood-2010-07-295238.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Diamond-BlackfanAnemia, MacrocyticAnimalsBenzothiazolesCell CycleCell LineageCell NucleolusChromosome DeletionChromosomes, Human, Pair 5Cyclin-Dependent Kinase Inhibitor p21Erythroid Precursor CellsHaploinsufficiencyHematopoiesisHumansImidazolesMiceMice, Inbred BALB CMyelodysplastic SyndromesPiperazinesProtein BindingProto-Oncogene Proteins c-mdm2Ribosomal ProteinsRNA, Small InterferingTolueneTumor Suppressor Protein p53ConceptsErythroid progenitor cellsDiamond-Blackfan anemiaMyelodysplastic syndromeProgenitor cellsInduction of p53Bone marrow biopsyErythroid lineageNuclear p53 stainingFailure of erythropoiesisBone marrow failureHuman erythroid progenitor cellsMarrow biopsyHematopoietic progenitor cellsP53 stainingHuman hematopoietic progenitor cellsCell cycle arrestPharmacologic inhibitionMarrow failureNutlin-3Consequent cell cycle arrestP53 pathwayCycle arrestSelective impairmentExpression of shRNAsP53
2009
Chapter 19 The Syndrome of Hypertension and Hyperkalemia (Pseudohypoaldosteronism Type II) WNK Kinases Regulate the Balance Between Renal Salt Reabsorption and Potassium Secretion
Kahle K, Wilson F, Lifton R. Chapter 19 The Syndrome of Hypertension and Hyperkalemia (Pseudohypoaldosteronism Type II) WNK Kinases Regulate the Balance Between Renal Salt Reabsorption and Potassium Secretion. 2009, 313-329. DOI: 10.1016/b978-0-12-449851-8.00019-x.ChaptersRenal potassium secretionLumen-negative potentialPotassium secretionPseudohypoaldosteronism type IINa-Cl cotransporterSalt reabsorptionDistal nephron potassium secretionPotassium channelsRenal outer medullary potassium channelENaC activitySyndrome of hypertensionPotential targetElectrogenic sodium reabsorptionPotassium channel ROMKDistal proton secretionRenal salt reabsorptionBK potassium channelsEpithelial sodium channelMolecular genetic discoveriesSodium reabsorptionWNK kinasesProfound hyperkalemiaImpaired productionMarked impairmentChannel ROMK
2007
WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo
Ring AM, Cheng SX, Leng Q, Kahle KT, Rinehart J, Lalioti MD, Volkman HM, Wilson FH, Hebert SC, Lifton RP. WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 4020-4024. PMID: 17360470, PMCID: PMC1805455, DOI: 10.1073/pnas.0611727104.Peer-Reviewed Original ResearchConceptsPseudohypoaldosteronism type IIDistal nephronPHAII-mutant WNK4Wild-type littermatesNa-Cl cotransporterAldosterone systemIntravascular volumeDistal colonSodium balanceElectrolyte homeostasisColonic epitheliumMajor mediatorDiverse mediatorsAltered activityENaC betaWNK4's inhibitionKinase activityIntact C-terminusPHAII-causing mutationsMiceWNK4MediatorsDownstream targetsWNK4 kinase activityENaCAn SGK1 site in WNK4 regulates Na+ channel and K+ channel activity and has implications for aldosterone signaling and K+ homeostasis
Ring AM, Leng Q, Rinehart J, Wilson FH, Kahle KT, Hebert SC, Lifton RP. An SGK1 site in WNK4 regulates Na+ channel and K+ channel activity and has implications for aldosterone signaling and K+ homeostasis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 4025-4029. PMID: 17360471, PMCID: PMC1803763, DOI: 10.1073/pnas.0611728104.Peer-Reviewed Original ResearchConceptsIntravascular volume depletionNa-Cl cotransporterAldosterone signalingPseudohypoaldosteronism type IIVolume depletionPhysiologic responsesNaCl reabsorptionPHAII-mutant WNK4Steroid hormone aldosteroneRenal outer medullaryRenal NaCl reabsorptionFunctional stateWNK4 mutationsROMK activityHormone aldosteroneOuter medullaryHyperkalemiaSecretionKidneyWild-type WNK4ReabsorptionAldosteroneChannel activityChannel ENaCWNK4
2006
WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1)
Leng Q, Kahle KT, Rinehart J, MacGregor GG, Wilson FH, Canessa CM, Lifton RP, Hebert SC. WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1). The Journal Of Physiology 2006, 571: 275-286. PMID: 16357011, PMCID: PMC1796803, DOI: 10.1113/jphysiol.2005.102202.Peer-Reviewed Original ResearchConceptsDistal convoluted tubuleInhibition of ROMK1KCNQ1/KCNE1Renal NaCl reabsorptionEpithelial sodium channelAmiloride-sensitive currentDistal nephronVivo effectsConvoluted tubulesKinase-dependent activationQT syndromeNCC activityNaCl reabsorptionNephron segmentsDuct principal cellsHereditary hypertensionSodium channelsPrincipal cellsII cellsRenal NaClSurface expressionXenopus laevis oocytesHypertensionHomeostatic systemDisease