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 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 target
2019
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
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