2022
Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer
Moutafi MK, Molero M, Morilla S, Baena J, Vathiotis IA, Gavrielatou N, Castro-Labrador L, de Garibay GR, Adradas V, Orive D, Valencia K, Calvo A, Montuenga LM, Aix S, Schalper KA, Herbst RS, Paz-Ares L, Rimm DL, Zugazagoitia J. Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e004757. PMID: 36002182, PMCID: PMC9413286, DOI: 10.1136/jitc-2022-004757.Peer-Reviewed Original ResearchConceptsProgression-free survivalPD-1 axis blockadePD-1 axis inhibitorsTumor proportion scoreCell lung cancerAxis blockadeQuantitative immunofluorescenceAxis inhibitionLung cancerCD44 levelsCD44 expressionTumor compartmentsLonger progression-free survivalAbsence of immunotherapyYale Cancer CenterWhole tissue sectionsQIF scoresExternal independent validationMost patientsOverall survivalTim-3Immune compartmentImmunotherapy strategiesPD-L1Untreated cohort
2013
An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance
Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, Nilsson MB, Gudikote J, Tran H, Cardnell RJ, Bearss DJ, Warner SL, Foulks JM, Kanner SB, Gandhi V, Krett N, Rosen ST, Kim ES, Herbst RS, Blumenschein GR, Lee JJ, Lippman SM, Ang KK, Mills GB, Hong WK, Weinstein JN, Wistuba II, Coombes KR, Minna JD, Heymach JV. An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance. Clinical Cancer Research 2013, 19: 279-290. PMID: 23091115, PMCID: PMC3567921, DOI: 10.1158/1078-0432.ccr-12-1558.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxl Receptor Tyrosine KinaseCarcinoma, Non-Small-Cell LungCell Line, TumorCluster AnalysisDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMiceNeoplasm MetastasisPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProteomeProteomicsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesRecurrenceReproducibility of ResultsConceptsEpithelial-mesenchymal transitionPotential therapeutic targetEGFR inhibitor resistanceTherapeutic targetEMT signatureInhibitor resistanceMesenchymal transition gene signatureMesenchymal cellsCell linesBiomarker-Integrated ApproachesPI3K/Akt pathway inhibitorNon-small cell lung carcinoma cell lineEGFR mutation statusReceptor tyrosine kinase AXLNSCLC cell linesPI3K/Akt inhibitorCell lung carcinoma cell lineGene expression profilesTyrosine kinase AXLLung carcinoma cell linePI3K inhibitorsDrug response analysisAkt pathway inhibitorCarcinoma cell linesErlotinib resistance
2012
Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist
Subbiah V, Brown RE, Buryanek J, Trent J, Ashkenazi A, Herbst R, Kurzrock R. Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist. Molecular Cancer Therapeutics 2012, 11: 2541-2546. PMID: 22914439, PMCID: PMC3496030, DOI: 10.1158/1535-7163.mct-12-0358.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBone NeoplasmsCell SurvivalChondrosarcomaDNA Mutational AnalysisHumansImmunohistochemistryIsocitrate DehydrogenaseLung NeoplasmsMaleMiddle AgedProteomicsProto-Oncogene Proteins c-bcl-2Radiography, ThoracicReceptors, Death DomainRecombinant ProteinsSignal TransductionTNF-Related Apoptosis-Inducing LigandTomography, X-Ray ComputedTreatment OutcomeConceptsRecombinant human Apo2L/TRAILApo2L/TRAILRecent computed tomography scanSustained partial responseEvidence of diseaseComputed tomography scanP-ERK 1/2Partial responseProgressive diseaseNF-κBp65Receptor agonistTomography scanSubcentimeter nodulesPatient tumorsMetastatic chondrosarcomaP-mTORPatientsProlonged responseP-STAT3Proapoptotic receptor agonistsChondrosarcomaBcl-2DulanerminLungTumors