2024
ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.
Hu B, Wiesehöfer M, de Miguel F, Liu Z, Chan L, Choi J, Melnick M, Arnal Estape A, Walther Z, Zhao D, Lopez-Giraldez F, Wurtz A, Cai G, Fan R, Gettinger S, Xiao A, Yan Q, Homer R, Nguyen D, Politi K. ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts. Cancer Research 2024, 84: 1303-1319. PMID: 38359163, PMCID: PMC11142404, DOI: 10.1158/0008-5472.can-23-0438.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsPatient-derived xenograftsEGFR mutant lung cancerMutant lung cancerPre-treatment tumorsResidual diseaseDrug toleranceLung cancerResidual tumor cells in vivoEGFR mutant lung adenocarcinomaTyrosine kinase inhibitor osimertinibEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitor treatmentTumor cells in vivoMutant lung adenocarcinomaMaximal tumor regressionTranscription factor Ascl1Drug-tolerant cellsTime of maximal responseEvidence of cellsCells in vivoOsimertinib treatmentTumor regressionSingle cell transcriptional profilingTumor cellsEGFR-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
2022
EP14.05-021 Promising Long-Term Survival after Surgical Resection of Early Stage Small Cell Lung Cancer in a Modern Single-Center Cohort
Ely S, Udelsman B, Homer R, Dhanasopon A, Woodard G. EP14.05-021 Promising Long-Term Survival after Surgical Resection of Early Stage Small Cell Lung Cancer in a Modern Single-Center Cohort. Journal Of Thoracic Oncology 2022, 17: s552-s553. DOI: 10.1016/j.jtho.2022.07.996.Peer-Reviewed Original ResearchDevelopment of an immunohistochemical assay for Siglec-15
Shafi S, Aung TN, Robbins C, Zugazagoitia J, Vathiotis I, Gavrielatou N, Yaghoobi V, Fernandez A, Niu S, Liu LN, Cusumano ZT, Leelatian N, Cole K, Wang H, Homer R, Herbst RS, Langermann S, Rimm DL. Development of an immunohistochemical assay for Siglec-15. Laboratory Investigation 2022, 102: 771-778. PMID: 35459795, PMCID: PMC9253057, DOI: 10.1038/s41374-022-00785-9.Peer-Reviewed Original ResearchConceptsSiglec-15IHC assaysPD-L1PD-1/PD-L1 inhibitionPD-L1 blockadePD-L1 inhibitionHigh expressionFuture clinical trialsImmunoglobulin-type lectinsSiglec-15 expressionCompanion diagnostic assayPromising new targetTumor histologyImmunotherapeutic targetLung cancerImmune cellsClinical trialsNovel recombinant antibodiesCancer histologyImmunohistochemical assaysMyeloid cellsTumor typesScoring systemNew targetsHigh concordance
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 targetEffectiveness of Thermal Ablation and Stereotactic Radiotherapy Based on Stage I Lung Cancer Histology
Uhlig J, Mehta S, Case MD, Dhanasopon A, Blasberg J, Homer RJ, Solomon SB, Kim HS. Effectiveness of Thermal Ablation and Stereotactic Radiotherapy Based on Stage I Lung Cancer Histology. Journal Of Vascular And Interventional Radiology 2021, 32: 1022-1028.e4. PMID: 33811997, DOI: 10.1016/j.jvir.2021.02.025.Peer-Reviewed Original ResearchConceptsStereotactic body radiotherapyStage I lung cancerI lung cancerOverall survivalHistological subtypesNeuroendocrine tumorsCell carcinomaLung cancerThermal ablationPropensity scoreMost histological subtypesNational Cancer DatabaseSignificant OS differenceAmerican Joint CommitteeLarge cell carcinomaSmall cell carcinomaHigher overall survivalSquamous cell carcinomaLung cancer histologyLung cancer variesSmall neuroendocrine tumorsMore comorbiditiesTA patientsCancer variesInitial treatment
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 inhibitorsDrug Sensitivity and Allele‐specificity of First‐line Osimertinib Resistance EGFR Mutations
Starrett J, Guernet A, Cuomo M, Poels K, van Rosenburgh I, Nagelberg A, Farnsworth D, Price K, Khan H, Ashtekar K, Gaefele M, Ayeni D, Stewart T, Kuhlmann A, Kaech S, Unni A, Homer R, Lockwood W, Michor F, Goldberg S, Lemmon M, Smith P, Cross D, Politi K. Drug Sensitivity and Allele‐specificity of First‐line Osimertinib Resistance EGFR Mutations. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.00612.Peer-Reviewed Original ResearchFirst-line osimertinibEGFR-mutant lung cancerMutant lung cancerOsimertinib treatmentEGFR-TKILung cancerEGFR mutationsTotal tumorsPreferred first-line therapySecondary mutationsThird-generation EGFR-TKIFirst-line osimertinib treatmentMichael Smith FoundationResistance EGFR mutationsFirst-line therapySecondary EGFR mutationGeneration EGFR-TKISubsequent treatment approachesTransgenic mouse modelLung cancer researchTumor volume changesCoronal MR imagesTumor volume measurementsNew Investigator AwardResistance mechanisms
2019
Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors
Ayeni D, Miller B, Kuhlmann A, Ho PC, Robles-Oteiza C, Gaefele M, Levy S, de Miguel FJ, Perry C, Guan T, Krystal G, Lockwood W, Zelterman D, Homer R, Liu Z, Kaech S, Politi K. Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors. Journal For ImmunoTherapy Of Cancer 2019, 7: 172. PMID: 31291990, PMCID: PMC6617639, DOI: 10.1186/s40425-019-0643-8.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsEGFR-mutant lung cancerMutant lung cancerTumor regressionErlotinib treatmentLung cancerImmune cellsLung tumorsMouse modelEffects of TKIsGrowth factor receptor tyrosine kinase inhibitorsTumor-infiltrating immune cellsDrug resistanceReceptor tyrosine kinase inhibitorsInflammatory immune cellsInflammatory T cellsEffect of erlotinibEGFR mutant lung tumorsInflammatory cellsImmunological profileT cellsCD40 agonistsImmunostimulatory effectsAlveolar macrophagesErlotinibReanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, Roden AC, Hirsch FR, Wistuba II, Pusztai L. Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer. Breast Cancer Research 2019, 21: 72. PMID: 31196152, PMCID: PMC6567382, DOI: 10.1186/s13058-019-1156-6.Peer-Reviewed Original ResearchConceptsPD-L1 expressionImmune cell PD-L1 expressionLung cancerImmune cellsTriple-negative breast cancerEasy scoring methodCompanion diagnostic testsPD-L1Immune therapyBreast cancerImmunohistochemical testsBetter outcomesLarger studyTumor cellsDiagnostic testsCancerExpression findingsCellsExpressionPoor agreementScoring methodTherapyTrials
2017
A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non–Small Cell Lung Cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, West WW, Wu H, Roden AC, Fujimoto J, Yu H, Anders R, Kowalewski A, Rivard C, Rehman J, Batenchuk C, Burns V, Hirsch FR, Wistuba II. A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non–Small Cell Lung Cancer. JAMA Oncology 2017, 3: 1051-1058. PMID: 28278348, PMCID: PMC5650234, DOI: 10.1001/jamaoncol.2017.0013.Peer-Reviewed Original ResearchConceptsPD-L1 expressionNon-small cell lung cancerDako Link 48 platformIntraclass correlation coefficientCell lung cancerImmune cellsPD-L1Tumor cellsSP142 antibodyLung cancerAnti-programmed cell death 1Less PD-L1 expressionCell death ligand 1Tumour cell assessmentPD-L1 antibodiesDeath ligand 1Cell death 1Cell scoringOwn scoring systemSerial histologic sectionsSP142 assayL1 therapyDeath-1Laboratory-developed testsPatient response
2015
Pathologists’ Staging of Multiple Foci of Lung Cancer
Homer RJ. Pathologists’ Staging of Multiple Foci of Lung Cancer. American Journal Of Clinical Pathology 2015, 143: 701-706. PMID: 25873504, DOI: 10.1309/ajcpnbwf55vgkoiw.Peer-Reviewed Original ResearchConceptsIntrapulmonary metastasesLung cancerLung carcinomaMultiple fociMultiple lung carcinomasPulmonary Pathology SocietySeparate primary tumorsLung cancer pathologyPrimary tumorPulmonary pathologyPathologic methodsIndependent primariesCancer pathologyPathologistsSelf-selected groupCarcinomaMetastasisCancerVoluntary surveyPathologySpecialty interestHistologyTumorsStaging
2014
Influence of Ground-glass Opacities on the Diagnostic Evaluation of Patients with Multiple Lung Cancers
Hall M, Maxfield M, Krechman A, Oliva I, Homer R, Boffa D, Detterbeck F, Kim A. Influence of Ground-glass Opacities on the Diagnostic Evaluation of Patients with Multiple Lung Cancers. Journal Of Surgical Research 2014, 186: 494. DOI: 10.1016/j.jss.2013.11.025.Peer-Reviewed Original ResearchThoracic Neoplasia: Carcinoma
Politi K, Dela Cruz C, Homer R. Thoracic Neoplasia: Carcinoma. 2014, 2677-2689. DOI: 10.1016/b978-0-12-386456-7.05310-7.ChaptersLung cancerLung cancer subtypesDifferent natural historyLung cancer biologyCancer deathMolecular subtypesMouse modelNew therapiesSurvival rateCancer subtypesNatural historyLung cancer genomeTumor samplesDiseaseCell linesCancer biologyTherapyOngoing studiesCancerSubtypesRecent knowledgeMolecular mechanismsSpecific subsetPatientsCarcinoma
2011
Molecular classification of nonsmall cell lung cancer using a 4‐protein quantitative assay
Anagnostou VK, Dimou AT, Botsis T, Killiam EJ, Gustavson MD, Homer RJ, Boffa D, Zolota V, Dougenis D, Tanoue L, Gettinger SN, Detterbeck FC, Syrigos KN, Bepler G, Rimm DL. Molecular classification of nonsmall cell lung cancer using a 4‐protein quantitative assay. Cancer 2011, 118: 1607-1618. PMID: 22009766, DOI: 10.1002/cncr.26450.Peer-Reviewed Original Research
2009
Regression of murine lung tumors by the let-7 microRNA
Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, Homer R, Brown D, Bader AG, Weidhaas JB, Slack FJ. Regression of murine lung tumors by the let-7 microRNA. Oncogene 2009, 29: 1580-1587. PMID: 19966857, PMCID: PMC2841713, DOI: 10.1038/onc.2009.445.Peer-Reviewed Original ResearchHigh Expression of Mammalian Target of Rapamycin Is Associated with Better Outcome for Patients with Early Stage Lung Adenocarcinoma
Anagnostou VK, Bepler G, Syrigos KN, Tanoue L, Gettinger S, Homer RJ, Boffa D, Detterbeck F, Rimm DL. High Expression of Mammalian Target of Rapamycin Is Associated with Better Outcome for Patients with Early Stage Lung Adenocarcinoma. Clinical Cancer Research 2009, 15: 4157-4164. PMID: 19509151, DOI: 10.1158/1078-0432.ccr-09-0099.Peer-Reviewed Original ResearchConceptsLung cancer patientsMTOR expressionCancer patientsMammalian targetEarly-stage lung adenocarcinomaHigh mTOR expressionIndependent lower riskMedian overall survivalStage IA patientsProtein expressionSubgroup of patientsLung adenocarcinoma patientsStage lung adenocarcinomaMTOR protein expressionRole of mTOROverall survivalPathologic characteristicsPatient survivalValidation cohortAdenocarcinoma groupAdenocarcinoma patientsPrognostic stratificationLung cancerTraining cohortFavorable outcome
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 riskPatientsAdenocarcinomaA SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk
Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, Muller RU, Straka E, Su L, Burki EA, Crowell RE, Patel R, Kulkarni T, Homer R, Zelterman D, Kidd KK, Zhu Y, Christiani DC, Belinsky SA, Slack FJ, Weidhaas JB. A SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk. Cancer Research 2008, 68: 8535-8540. PMID: 18922928, PMCID: PMC2672193, DOI: 10.1158/0008-5472.can-08-2129.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCase-control studyLung cancer riskIndependent case-control studiesLung cancerSingle nucleotide polymorphismsCancer riskNon-small cell lung cancer riskCell lung cancer riskVariant allelesCell lung cancerKRAS 3' untranslated regionLung cancer susceptibilityUnidentified single-nucleotide polymorphismsNSCLC patientsModerate smokersNSCLC cancerNSCLC casesCancer deathKRAS overexpressionCancerCancer susceptibilityOncogene expressionPatientsRisk