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
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