0000000000135204

AUTHOR

Matthew D. Wilkerson

showing 2 related works from this author

Integrative genomic and proteomic analyses identify targets for Lkb1 deficient metastatic lung tumors

2010

SummaryIn mice, Lkb1 deletion and activation of KrasG12D results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathw…

ProteomicsCancer ResearchLung NeoplasmsMAP Kinase Kinase 2MAP Kinase Kinase 1CELLCYCLEAMP-Activated Protein Kinasesmedicine.disease_causeMice0302 clinical medicineAMP-Activated Protein Kinase KinasesCell MovementCarcinoma Non-Small-Cell LungEnzyme InhibitorsNeoplasm MetastasisPhosphorylationLymph nodePhosphoinositide-3 Kinase Inhibitors0303 health sciencesTOR Serine-Threonine KinasesIntracellular Signaling Peptides and ProteinsGenomicsCell cycleProtein-Tyrosine KinasesPenetrance3. Good healthUp-RegulationGene Expression Regulation Neoplasticmedicine.anatomical_structuresrc-Family KinasesOncologySIGNALING030220 oncology & carcinogenesisDrug Therapy CombinationFemaleRNA InterferenceKRASSignal TransductionMice NudeBiologyProtein Serine-Threonine KinasesArticleProto-Oncogene Proteins p21(ras)03 medical and health sciencesCell Line TumorProto-Oncogene ProteinsmedicineCell AdhesionAnimalsHumansEpithelial–mesenchymal transitionProtein Kinase Inhibitors030304 developmental biologyFocal AdhesionsGene Expression ProfilingCell BiologyXenograft Model Antitumor AssaysMice Mutant StrainsGene expression profilingFocal Adhesion Protein-Tyrosine KinasesCancer cellCell TransdifferentiationCancer researchras ProteinsCarcinogenesis
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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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