2023
Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma
Berko E, Witek G, Matkar S, Petrova Z, Wu M, Smith C, Daniels A, Kalna J, Kennedy A, Gostuski I, Casey C, Krytska K, Gerelus M, Pavlick D, Ghazarian S, Park J, Marachelian A, Maris J, Goldsmith K, Radhakrishnan R, Lemmon M, Mossé Y. Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma. Nature Communications 2023, 14: 2601. PMID: 37147298, PMCID: PMC10163008, DOI: 10.1038/s41467-023-38195-0.Peer-Reviewed Original ResearchConceptsAnaplastic lymphoma kinaseLorlatinib resistanceTumor DNAPhase 1 trialCirculating tumor DNAPre-clinical studiesResistance mechanismsTumor DNA samplesALK mutationsDisease progressionHeterogeneity of tumorsClinical utilityRAS-MAPK pathwayTherapeutic strategiesLymphoma kinasePatientsResistance mutationsNeuroblastomaProgressionTrialsMutationsBiochemical assaysDNA samplesPoint mutationsLorlatinibEfficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations
Grant M, Aredo J, Starrett J, Stockhammer P, van Rosenburgh I, Wurtz A, Piper-Valillo A, Piotrowska Z, Falcon C, Yu H, Aggarwal C, Scholes D, Patil T, Nguyen C, Phadke M, Li F, Neal J, Lemmon M, Walther Z, Politi K, Goldberg S. Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations. Clinical Cancer Research 2023, 29: of1-of8. PMID: 36913537, PMCID: PMC10493186, DOI: 10.1158/1078-0432.ccr-22-3497.Peer-Reviewed Original ResearchConceptsProgression-free survivalNon-small cell lung cancerInferior progression-free survivalMulticenter retrospective cohortEfficacy of osimertinibMulti-institutional cohortCell lung cancerExon 19 deletion mutationUncommon EGFRRetrospective cohortClinical outcomesClinical efficacyLung cancerOsimertinib efficacyEGFR mutationsPreclinical modelsEx19delPatientsAACR Genie databaseLater linesOsimertinibMutant cohortFirst lineCohortEfficacy
2022
Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations
van Alderwerelt van Rosenburgh I, Lu D, Grant M, Stayrook S, Phadke M, Walther Z, Goldberg S, Politi K, Lemmon M, Ashtekar K, Tsutsui Y. Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations. Nature Communications 2022, 13: 6791. PMID: 36357385, PMCID: PMC9649653, DOI: 10.1038/s41467-022-34398-z.Peer-Reviewed Original Research
2013
Mechanism for activation of mutated epidermal growth factor receptors in lung cancer
Brewer M, Yun CH, Lai D, Lemmon MA, Eck MJ, Pao W. Mechanism for activation of mutated epidermal growth factor receptors in lung cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: e3595-e3604. PMID: 24019492, PMCID: PMC3780914, DOI: 10.1073/pnas.1220050110.Peer-Reviewed Original ResearchConceptsWT epidermal growth factor receptorEpidermal growth factor receptorTyrosine kinase domainGrowth factor receptorConformational changesAsymmetric dimer interfaceMutant epidermal growth factor receptorAllosteric conformational changeAsymmetric dimer formationFactor receptorIntermolecular regulationKinase domainEGFR tyrosine kinase domainDimer interfaceMutantsM mutantActive conformation
2012
Occupy EGFR
Park JH, Lemmon MA. Occupy EGFR. Cancer Discovery 2012, 2: 398-400. PMID: 22588876, PMCID: PMC3354646, DOI: 10.1158/2159-8290.cd-12-0144.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsErbB ReceptorsErlotinib HydrochlorideGliomaHumansLung NeoplasmsProtein Kinase InhibitorsQuinazolinesConceptsEpidermal growth factor receptor (EGFR) mutationsNon-small cell lung cancer (NSCLC) tumorsCell lung cancer tumorsDifferent EGFR mutationsTreatment of glioblastomaLung cancer tumorsDistinct receptor conformationsEGFR mutationsReceptor mutationsEGFR inhibitorsCancer tumorsInhibitor efficacyEGFR mutantsEGFR variantsEGFRGlioblastomaDrug selectivityReceptor conformationNew studiesBarkovichErlotinibGefitinibTumors
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