2024
EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.
Kuhlmann-Hogan A, Cordes T, Xu Z, Kuna R, Traina K, Robles-Oteiza C, Ayeni D, Kwong E, Levy S, Globig A, Nobari M, Cheng G, Leibel S, Homer R, Shaw R, Metallo C, Politi K, Kaech S. EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth. Cancer Discovery 2024, 14: 524-545. PMID: 38241033, PMCID: PMC11258210, DOI: 10.1158/2159-8290.cd-23-0434.Peer-Reviewed Original ResearchLung adenocarcinomaGM-CSFEGFR-mutant lung adenocarcinomaGM-CSF secretionProinflammatory immune responseSuppress tumor progressionLocal immunosuppressionStatin therapyTherapeutic combinationsNovel therapiesTumor cellsTumor progressionTumor growthLung adenocarcinoma cellsEGFR phosphorylationImmune responseTransformed epitheliumCancer cellsInflammatory functionsEGFR signalingMacrophage metabolismAlveolar macrophagesIncreased cholesterol synthesisMetabolic supportOncogenic signalingEGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth.
Kuhlmann-Hogan A, Cordes T, Xu Z, Kuna R, Traina K, Robles-Oteíza C, Ayeni D, Kwong E, Levy S, Globig A, Nobari M, Cheng G, Leibel S, Homer R, Shaw R, Metallo C, Politi K, Kaech S. EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth. Cancer Discovery 2024, of1-of22. PMID: 38270272, DOI: 10.1158/2159-8290.cd-23-0434.Peer-Reviewed Original ResearchLung adenocarcinomaGM-CSFEGFR-mutant lung adenocarcinomaT cell-based immunotherapyTransformed epitheliumOncogenic signalingGM-CSF secretionProinflammatory immune responseSuppress tumor progressionLocal immunosuppressionStatin therapyTherapeutic combinationsNovel therapiesTumor cellsTumor progressionTumor growthLung cancerLung adenocarcinoma cellsEGFR phosphorylationImmune responseImmunological supportCancer cellsInflammatory functionsAlveolar macrophagesIncreased cholesterol synthesis
2021
Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma
Robles-Oteiza C, Ayeni D, Levy S, Homer RJ, Kaech SM, Politi K. Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma. Disease Models & Mechanisms 2021, 14: dmm049072. PMID: 34494649, PMCID: PMC8617309, DOI: 10.1242/dmm.049072.Peer-Reviewed Original ResearchConceptsHuman diphtheria toxin receptorDiphtheria toxin receptorTumor regressionEGFR-mutant lung cancerEGFR-mutant lung adenocarcinomaEGFR-mutant tumorsMutant EGFRTissue-specific promotorsFVB miceLung cancerSystemic administrationLung adenocarcinomaMurine lungRapid regressionConditional ablationTumor cellsUpregulated expressionMiceElevated expressionToxin receptorHB-EGFCell populationsHBEGFEGFRPrimary targetGenetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma
Foggetti G, Li C, Cai H, Hellyer JA, Lin WY, Ayeni D, Hastings K, Choi J, Wurtz A, Andrejka L, Maghini DG, Rashleigh N, Levy S, Homer R, Gettinger SN, Diehn M, Wakelee HA, Petrov DA, Winslow MM, Politi K. Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma. Cancer Discovery 2021, 11: 1736-1753. PMID: 33707235, PMCID: PMC8530463, DOI: 10.1158/2159-8290.cd-20-1385.Peer-Reviewed Original ResearchConceptsSuppressor geneKey tumor suppressorPutative tumor suppressor geneTumor suppressor geneSensitivity of EGFRTumor growthOncogenic contextTumor suppressorHuman EGFRGenetic determinantsKeap1 pathwayComplex genotypesTumor suppressor gene alterationsLung cancer growthGenesDeficient lung adenocarcinomaLung adenocarcinomaGenetic alterationsIssue featureStrong driverCancer growthEGFR inhibitorsKinase inhibitorsInactivationGene alterations
2020
Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations
Starrett JH, Guernet AA, Cuomo ME, Poels KE, van Alderwerelt van Rosenburgh IK, Nagelberg A, Farnsworth D, Price KS, Khan H, Ashtekar KD, Gaefele M, Ayeni D, Stewart TF, Kuhlmann A, Kaech S, Unni AM, Homer R, Lockwood WW, Michor F, Goldberg SB, Lemmon MA, Smith PD, Cross D, Politi K. Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations. Cancer Research 2020, 80: 2017-2030. PMID: 32193290, PMCID: PMC7392201, DOI: 10.1158/0008-5472.can-19-3819.Peer-Reviewed Original ResearchConceptsOsimertinib resistancePreferred first-line therapyThird-generation EGFR tyrosine kinase inhibitorEGFR tyrosine kinase inhibitorsResistance EGFR mutationsFirst-line therapyMutant lung cancerFirst-line osimertinibSubsequent treatment approachesTransgenic mouse modelTyrosine kinase inhibitorsSecondary mutationsErlotinib treatmentLung cancerEGFR mutationsLung adenocarcinomaMouse modelTherapeutic strategiesTherapeutic testingTreatment approachesMutant tumorsResistance mutationsDrug sensitivityDriver mutationsKinase inhibitors
2013
Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma
Cai G, Wong R, Chhieng D, Levy GH, Gettinger SN, Herbst RS, Puchalski JT, Homer RJ, Hui P. Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma. Cancer Cytopathology 2013, 121: 500-507. PMID: 23495083, DOI: 10.1002/cncy.21288.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseBiomarkers, TumorBone NeoplasmsCytodiagnosisDNA, NeoplasmErbB ReceptorsFeasibility StudiesFemaleGene RearrangementHumansIn Situ Hybridization, FluorescenceLiver NeoplasmsLung NeoplasmsMaleMiddle AgedMutationNeoplasm Recurrence, LocalPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsReal-Time Polymerase Chain ReactionReceptor Protein-Tyrosine KinasesSoft Tissue NeoplasmsYoung AdultConceptsALK gene rearrangementMetastatic lung adenocarcinomaEGFR mutationsKRAS mutationsMetastatic tumorsEpidermal growth factor receptorLung adenocarcinomaCytological specimensGene rearrangementsMolecular testsMolecular alterationsKirsten rat sarcoma viral oncogene homolog (KRAS) mutationsALK gene rearrangement analysisAnaplastic lymphoma kinase (ALK) gene rearrangementEGFR T790M mutationRat sarcoma viral oncogene homolog mutationsCases of lungT790M mutationImportant therapeutic implicationsFine needle aspiratesGene rearrangement analysisCell block materialGrowth factor receptorRecurrent lungRecurrent adenocarcinoma
2008
Thyroid Transcription Factor 1 Is an Independent Prognostic Factor for Patients With Stage I Lung Adenocarcinoma
Anagnostou VK, Syrigos KN, Bepler G, Homer RJ, Rimm DL. Thyroid Transcription Factor 1 Is an Independent Prognostic Factor for Patients With Stage I Lung Adenocarcinoma. Journal Of Clinical Oncology 2008, 27: 271-278. PMID: 19064983, DOI: 10.1200/jco.2008.17.0043.Peer-Reviewed Original ResearchConceptsThyroid transcription factor-1Stage I lung adenocarcinomaTTF1 expressionTranscription factor 1Lung adenocarcinomaStage IIndependent lower riskMedian overall survivalProtein expressionIndependent prognostic factorPotential prognostic parametersSubgroup of patientsFactor 1Overall survivalPrognostic factorsPatient survivalPrognostic parametersPrognostic stratificationLung cancerFavorable outcomeSitu protein expressionIndependent cohortLower riskPatientsAdenocarcinoma