0000000000634451

AUTHOR

Jacob B. Reibel

showing 3 related works from this author

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

2013

Abstract The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased CTLs and increased markers of T-cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T-cell function and lowering the levels of tumor-promoting cytokines. Expression of m…

Lung NeoplasmsT-LymphocytesT cellProgrammed Cell Death 1 ReceptorMice TransgenicLymphocyte ActivationB7-H1 AntigenArticleCell LineProinflammatory cytokineMiceCarcinoma Non-Small-Cell LungTumor MicroenvironmentmedicineAnimalsHumansCytotoxic T cellEpidermal growth factor receptorLung cancerEGFR inhibitorsTumor microenvironmentbiologyOncogenesmedicine.diseaseErbB ReceptorsGene Expression Regulation NeoplasticMice Inbred C57BLmedicine.anatomical_structureOncologyTumor EscapeImmunologyCancer researchbiology.proteinCytokinesTumor EscapeSignal TransductionCancer Discovery
researchProduct

Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor.

2014

Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and the identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library, we observe that SCLC is sensitive to transcription-targeting drugs, in particular to THZ1, a recently identified covalent inhibitor of cyclin-dependent kinase 7. We find that expression of super-enhancer-associated transcription factor genes, including MYC family proto-oncogenes and neuroendocrine lineage-specific factors, is highly vulnerability to THZ1 treatment. We propose that downregulation of these transcription factors contribut…

Cancer ResearchLung NeoplasmsTranscription GeneticMolecular Sequence DataAntineoplastic AgentsBiologyBioinformaticsArticleMiceSuper-enhancerDownregulation and upregulationCell Line TumorMedicineAnimalsHumansEnzyme InhibitorsneoplasmsTranscription factorRegulation of gene expressionbusiness.industryCell BiologyNeoplasms ExperimentalSequence Analysis DNASmall Cell Lung CarcinomaXenograft Model Antitumor AssayshumanitiesCyclin-Dependent Kinasesrespiratory tract diseasesHigh-Throughput Screening AssaysGene Expression Regulation NeoplasticOncologyCovalent bondCancer cellCancer researchNon small cellSmall Cell Lung CarcinomaCyclin-dependent kinase 7businessTranscription Factor GeneCDK12Transcription FactorsCancer cell
researchProduct

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer.

2016

Abstract As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcrip…

0301 basic medicineModels MolecularLung Neoplasmsmedicine.medical_treatmentMolecular ConformationGene ExpressionAntineoplastic Agentsmacromolecular substancesBiologymedicine.disease_causeArticleMalignant transformationTargeted therapy03 medical and health sciencesMiceStructure-Activity RelationshipCell Line TumormedicineAnimalsHumansEnhancer of Zeste Homolog 2 ProteinMolecular Targeted TherapyLung cancerPromoter Regions GeneticGene Expression ProfilingEZH2Cancermedicine.diseaseMagnetic Resonance ImagingXenograft Model Antitumor AssaysChromatinrespiratory tract diseasesGene Expression Regulation NeoplasticDisease Models Animal030104 developmental biologyCell Transformation NeoplasticEnhancer Elements GeneticOncologyDrug DesignCancer researchAdenocarcinomaKRASEpigenetic therapyCancer discovery
researchProduct