2016
Overcoming resistance to HER2 inhibitors through state-specific kinase binding
Novotny CJ, Pollari S, Park JH, Lemmon MA, Shen W, Shokat KM. Overcoming resistance to HER2 inhibitors through state-specific kinase binding. Nature Chemical Biology 2016, 12: 923-930. PMID: 27595329, PMCID: PMC5069157, DOI: 10.1038/nchembio.2171.Peer-Reviewed Original ResearchThe ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma
Infarinato NR, Park JH, Krytska K, Ryles HT, Sano R, Szigety KM, Li Y, Zou HY, Lee NV, Smeal T, Lemmon MA, Mossé YP. The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Cancer Discovery 2016, 6: 96-107. PMID: 26554404, PMCID: PMC4707106, DOI: 10.1158/2159-8290.cd-15-1056.Peer-Reviewed Original ResearchMeSH KeywordsAminopyridinesAnaplastic Lymphoma KinaseAnimalsCell Line, TumorCrizotinibDrug Resistance, NeoplasmHumansLactamsLactams, MacrocyclicMiceMutationNeuroblastomaPhosphorylationProtein Kinase InhibitorsPyrazolesPyridinesReceptor Protein-Tyrosine KinasesTreatment OutcomeXenograft Model Antitumor AssaysConceptsAnaplastic lymphoma kinaseCrizotinib resistancePF-06463922ALK variantsTreatment of patientsALK inhibitor crizotinibPatient-derived xenograftsXenograft mouse modelPreclinical rationaleClinical obstacleNeuroblastoma modelClinical trialsTumor regressionPrimary resistanceInhibitor crizotinibXenograft tumorsMouse modelXenograft modelLymphoma kinaseNeuroblastomaCrizotinibHigh potencyF1174LVivo dataImproved potency
2012
Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma
Carpenter EL, Haglund EA, Mace EM, Deng D, Martinez D, Wood AC, Chow AK, Weiser DA, Belcastro LT, Winter C, Bresler SC, Asgharzadeh S, Seeger R, Zhao H, Guo R, Christensen J, Orange J, Pawel B, Lemmon M, Mossé Y. Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma. Oncogene 2012, 31: 4859-4867. PMID: 22266870, PMCID: PMC3730824, DOI: 10.1038/onc.2011.647.Peer-Reviewed Original ResearchMeSH KeywordsAnaplastic Lymphoma KinaseAntibodies, MonoclonalAntigens, NeoplasmCell DeathCell Line, TumorCell ProliferationCrizotinibHumansMutationNeuroblastomaPhosphorylationProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-metPyrazolesPyridinesReceptor Protein-Tyrosine KinasesSignal TransductionConceptsAnaplastic lymphoma kinaseLymphoma kinaseHuman neuroblastomaSmall molecule tyrosine kinase inhibitorsAntibody-dependent cellular cytotoxicityReceptor tyrosine kinasesDevastating pediatric cancerSympathetic nervous systemALK inhibitor crizotinibComplementary therapeutic approachALK-positive tumorsPromising therapeutic strategyTyrosine kinase inhibitorsAntibody-induced growth inhibitionCell linesTractable therapeutic targetWild-type ALKTyrosine kinaseALK aberrationsNeuroblastoma patientsLung cancerALK mutationsInhibitor crizotinibCellular cytotoxicityALK antibody
2011
Differential Inhibitor Sensitivity of Anaplastic Lymphoma Kinase Variants Found in Neuroblastoma
Bresler SC, Wood AC, Haglund EA, Courtright J, Belcastro LT, Plegaria JS, Cole K, Toporovskaya Y, Zhao H, Carpenter EL, Christensen JG, Maris JM, Lemmon MA, Mossé YP. Differential Inhibitor Sensitivity of Anaplastic Lymphoma Kinase Variants Found in Neuroblastoma. Science Translational Medicine 2011, 3: 108ra114. PMID: 22072639, PMCID: PMC3319004, DOI: 10.1126/scitranslmed.3002950.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnaplastic Lymphoma KinaseCell Line, TumorCrizotinibDrug Resistance, NeoplasmGenome, HumanHumansKineticsModels, MolecularMutant ProteinsMutationNeuroblastomaPhosphorylationProtein Kinase InhibitorsProtein Structure, TertiaryPyrazolesPyridinesReceptor Protein-Tyrosine Kinases
2006
EGF-independent activation of cell-surface EGF receptors harboring mutations found in gefitinib-sensitive lung cancer
Choi SH, Mendrola JM, Lemmon MA. EGF-independent activation of cell-surface EGF receptors harboring mutations found in gefitinib-sensitive lung cancer. Oncogene 2006, 26: 1567-1576. PMID: 16953218, DOI: 10.1038/sj.onc.1209957.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorTyrosine kinase domainKinase domainEGF receptorRecent structural studiesSomatic mutationsCell surface EGF receptorsTyrosine kinase activityAbsence of EGFAutoinhibitory interactionsActivation loopErbB family membersGrowth factor receptorTyrosine phosphorylationEGFR tyrosine kinase domainKinase activityNull backgroundMechanistic basisOncogenic mutationsBiochemical propertiesCell surfaceCell lung carcinoma patientsFactor receptorMutationsLung carcinoma patients