2024
Detecting small cell transformation in patients with advanced EGFR mutant lung adenocarcinoma through epigenomic cfDNA profiling
Zarif T, Meador C, Qiu X, Seo J, Davidsohn M, Savignano H, Lakshminarayanan G, McClure H, Canniff J, Fortunato B, Li R, Banwait M, Semaan K, Eid M, Long H, Hung Y, Mahadevan N, Barbie D, Oser M, Piotrowska Z, Choueiri T, Baca S, Hata A, Freedman M, Berchuck J. Detecting small cell transformation in patients with advanced EGFR mutant lung adenocarcinoma through epigenomic cfDNA profiling. Clinical Cancer Research 2024, 30: 3798-3811. PMID: 38912901, PMCID: PMC11369616, DOI: 10.1158/1078-0432.ccr-24-0466.Peer-Reviewed Original ResearchConceptsEGFR mutant lung adenocarcinomaSmall cell lung cancerSmall cell transformationLung cancer patient-derived xenograftPatient-derived xenograftsLung adenocarcinomaEGFR mutantsChIP-seqEpigenomic featuresMeDIP-seqImmunoprecipitation sequencingCell transformationHistological transformation to small cell lung cancerTransformation to small cell lung cancerMethylated DNA immunoprecipitation sequencingTransposase-accessible chromatin sequencingH3K27ac ChIP-seqMechanisms of treatment resistanceChromatin immunoprecipitation sequencingHistone modification H3K27acMutant lung adenocarcinomaCell lung cancerChromatin accessibilityChromatin sequencingEpigenomic landscapeASCL1 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, 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 cells
2017
Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up
Kadara H, Choi M, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Yoo Y, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Wistuba II, Herbst RS. Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up. Annals Of Oncology 2017, 28: 75-82. PMID: 27687306, PMCID: PMC5982809, DOI: 10.1093/annonc/mdw436.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalPoor recurrence-free survivalWhole-exome sequencingEarly-stage lung adenocarcinomaMutant lung adenocarcinomaLung adenocarcinomaImmune markersClinical outcomesExact testNatural killer cell infiltrationProportional hazards regression modelsGranzyme B levelsImmune marker analysisImmune profiling analysisPD-L1 expressionImmune-based therapiesTumoral PD-L1Hazards regression modelsKRAS mutant tumorsNormal lung tissuesMajority of deathsFisher's exact testHigh mutation burdenAnalysis of immunophenotypeRelevant molecular markers
2016
Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma
Metz H, Kargl J, Busch S, Kim K, Kurland B, Abberbock S, Randolph-Habecker J, Knoblaugh S, Kolls J, White M, Houghton A. Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8795-8800. PMID: 27439864, PMCID: PMC4978299, DOI: 10.1073/pnas.1601989113.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Janus kinase/signal transducerKinase/signal transducerTumor burdenActivator of transcriptionReceptor substrate-1IRS-1 deficiencyKRAS-mutant lung adenocarcinomaInsulin-like growth factor receptorAdenoviral Cre recombinaseIL-22 receptorMutant lung adenocarcinomaTumor-promoting inflammationAdaptor proteinSignificant survival disadvantageGrowth factor receptorSignal transducerSubstrate-1PI3KProinflammatory phenotypeLung cancerLung adenocarcinomaMutant subgroupTissue microarrayCre recombinaseImpact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases
Magnuson WJ, Yeung JT, Guillod PD, Gettinger SN, Yu JB, Chiang VL. Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases. International Journal Of Radiation Oncology • Biology • Physics 2016, 95: 673-679. PMID: 27034176, DOI: 10.1016/j.ijrobp.2016.01.037.Peer-Reviewed Original ResearchConceptsWhole-brain radiation therapyUpfront EGFR-TKIIntracranial progression-free survivalUpfront radiation therapyProgression-free survivalBrain metastasesEGFR-TKI groupEGFR-TKIEGFR-mutant NSCLCOverall survivalRadiation therapyEpidermal Growth Factor Receptor–Mutant NonDisease-specific Graded Prognostic AssessmentUpfront EGFR tyrosine kinase inhibitorsEGFR-TKI resistance mutationSmall cell lung cancerEGFR tyrosine kinase inhibitorsEGFR-TKI useMedian overall survivalSimilar overall survivalUpfront RT groupInferior overall survivalCell lung cancerMutant lung adenocarcinomaEpidermal growth factor receptor
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