0000000000634454

AUTHOR

Abigail Altabef

showing 4 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
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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
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Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a target in LKB1 Mutant Lung Cancer

2013

Abstract The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non–small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetica…

DNA Replicationcongenital hereditary and neonatal diseases and abnormalitiesLung NeoplasmsMutantSTK11BiologyAMP-Activated Protein KinasesProtein Serine-Threonine Kinasesmedicine.disease_causeArticleProto-Oncogene Proteins p21(ras)MiceDeoxythymidylate kinaseAMP-Activated Protein Kinase KinasesRNA interferenceCell Line TumorCarcinoma Non-Small-Cell LungmedicineMetabolomicsThymine NucleotidesAnimalsHumansMolecular Targeted TherapyLung cancerskin and connective tissue diseasesCell DeathModels GeneticKinaseCell growthGenomicsmedicine.diseaseMolecular biologyHigh-Throughput Screening AssaysOncologyGene Knockdown TechniquesCancer researchRNA InterferenceKRASNucleoside-Phosphate KinaseDNA Damage
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Abstract B290: Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors.

2013

Abstract The recent clinical success of therapeutic blockade of the immune checkpoint Programmed Death (PD)-1 in advanced lung cancer patients suggests that mechanisms of immune escape may contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a gene signature indicative of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4) and multiple tumor-promoting inflammatory cytokines. Accordingly, we identified a decrease in the number of cytotoxic T cells and an increase in markers of T cell exhaustion in genetically engineered mouse models (GEMMs) of EGFR-driven lu…

Cancer ResearchTumor microenvironmentbiologyCell growthT cellCancermedicine.diseaseImmune checkpointmedicine.anatomical_structureOncologyImmunologybiology.proteinmedicineCytotoxic T cellEpidermal growth factor receptorLung cancerMolecular Cancer Therapeutics
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