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 cells
2022
Functional Analysis of MET Exon 14 Skipping Alteration in Cancer Invasion and Metastatic DisseminationMET Exon 14 Skipping Alteration Promotes Metastasis
Wang F, Liu Y, Qiu W, Shum E, Feng M, Zhao D, Zheng D, Borczuk A, Cheng H, Halmos B. Functional Analysis of MET Exon 14 Skipping Alteration in Cancer Invasion and Metastatic DisseminationMET Exon 14 Skipping Alteration Promotes Metastasis. Cancer Research 2022, 82: 1365-1379. PMID: 35078819, DOI: 10.1158/0008-5472.can-21-1327.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerMetastasis in vivoLung cancerInvasive capacity in vitroExtracellular matrix disassemblyReceptor kinase activityTumor progression of non-small cell lung cancerRNA sequencing analysisImpaired receptor internalizationTreatment of lung cancerMetastasis-related pathwaysCell lung cancerMolecular mechanisms of actionCytoskeleton remodelingEndocytic degradationSequence analysisCell scatteringEffective treatment of lung cancerPotential therapeutic optionCRISPR editingCell movementKinase activityMechanistic functionProgression of non-small cell lung cancerMatrix disassembly
2021
A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancer