2024
Update on Biomarkers in Renal Cell Carcinoma.
Saliby R, Saad E, Kashima S, Schoenfeld D, Braun D. Update on Biomarkers in Renal Cell Carcinoma. American Society Of Clinical Oncology Educational Book 2024, 44: e430734. PMID: 38207251, DOI: 10.1200/edbk_430734.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRenal cell carcinomaCell carcinomaMetastatic renal cell carcinomaTumor intrinsic featuresImmune checkpoint inhibitorsRobust predictive biomarkersCheckpoint inhibitorsDurable responsesOverall survivalCare regimensPathological characteristicsPredictive biomarkersTherapeutic responseTreatment paradigmImmune systemHost factorsTranscriptional signatureGenomic alterationsTumor heterogeneityBiomarkersCarcinomaBiomarker discoveryInnovative technological approachesRegimens
2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysisImmune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Schoenfeld D, Moutafi M, Martinez S, Djureinovic D, Merkin R, Adeniran A, Braun D, Signoretti S, Choueiri T, Parisi F, Hurwitz M, Rimm D, Wei W, Jilaveanu L, Kluger H. Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases. Journal For ImmunoTherapy Of Cancer 2023, 11: e007240. PMID: 37586773, PMCID: PMC10432651, DOI: 10.1136/jitc-2023-007240.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaBrain metastasesPrimary tumorTumor microenvironmentDigital spatial profilingCell carcinomaActivation protein expressionInflammatory macrophage markersRCC brain metastasesInnate immune activatorsNormal kidney samplesProgressive stagesExtracranial metastasesTim-3Immune checkpointsImmune dysfunctionImmune activationRCC metastasisLonger survivalImmune activatorsMacrophage markersTreatment responseSeparate cohortTissue microarrayMetastatic samplesResponse to "NLRC5 germline variants and their potential role in eliciting an immune response in patients with cancer treated with immune checkpoint inhibitors" by Xiang-Yu Meng
Aizenbud L, Schoenfeld D, Caulfield J, Mann J, Austin M, Perdigoto A, Herold K, Kluger H. Response to "NLRC5 germline variants and their potential role in eliciting an immune response in patients with cancer treated with immune checkpoint inhibitors" by Xiang-Yu Meng. Journal For ImmunoTherapy Of Cancer 2023, 11: e007397. PMID: 37349129, PMCID: PMC10314693, DOI: 10.1136/jitc-2023-007397.Peer-Reviewed Original ResearchOutcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma
Dizman N, Austin M, Considine B, Jessel S, Schoenfeld D, Merl M, Hurwitz M, Sznol M, Kluger H. Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 21: 221-229. PMID: 36681606, DOI: 10.1016/j.clgc.2023.01.002.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaPembrolizumab/axitinibObjective response rateProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalAdverse eventsRenal cell carcinomaCell carcinomaClear cell metastatic renal cell carcinomaVascular endothelial growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsCombination immune checkpoint inhibitorsGrade 5 adverse eventsPrior immune checkpoint inhibitorsSuperior progression-free survivalReceptor tyrosine kinase inhibitorsYale-New Haven HospitalFurther-line treatmentNivolumab/ipilimumabRECIST 1.1 criteriaResponse-evaluable patientsDisease control rateSecond-line therapyFirst-line treatment
2022
Loss of PBRM1 alters promoter histone modifications and activates ALDH1A1 to drive renal cell carcinomaPBRM1 loss increases H3K4me3 marks and expression of ALDH1A1
Schoenfeld D, Zhou R, Zairis S, Su W, Steinbach N, Mathur D, Bansal A, Zachem A, Tavarez B, Hasson D, Bernstein E, Rabadan R, Parsons R. Loss of PBRM1 alters promoter histone modifications and activates ALDH1A1 to drive renal cell carcinomaPBRM1 loss increases H3K4me3 marks and expression of ALDH1A1. Molecular Cancer Research 2022, 20: 1193-1207. PMID: 35412614, PMCID: PMC9357026, DOI: 10.1158/1541-7786.mcr-21-1039.Peer-Reviewed Original ResearchConceptsRetinoic acid biosynthesisSuch target genesPromoter histone modificationsAcid biosynthesisHistone modificationsClear cell renal cell carcinomaTarget genesLoss of PBRM1SWI/SNF complexSWI/SNF chromatinSWI/SNF subunitsHistone modification ChIP-seqSWI/SNF componentsATAC-seq dataCcRCC cell linesDe novo gainPBAF subunitsH3K4me3 peaksH3K4me3 marksPBAF complexSNF complexEpigenomic approachesChIP-seqRNA-seqHigh mutation frequency
2015
PTEN inhibits PREX2-catalyzed activation of RAC1 to restrain tumor cell invasion
Mense SM, Barrows D, Hodakoski C, Steinbach N, Schoenfeld D, Su W, Hopkins BD, Su T, Fine B, Hibshoosh H, Parsons R. PTEN inhibits PREX2-catalyzed activation of RAC1 to restrain tumor cell invasion. Science Signaling 2015, 8: ra32. PMID: 25829446, PMCID: PMC4874664, DOI: 10.1126/scisignal.2005840.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCell MovementDNA PrimersFluorescent Antibody TechniqueGene Knockout TechniquesGenetic VectorsGuanine Nucleotide Exchange FactorsHumansImmunoblottingImmunoprecipitationLentivirusMiceNeoplasm InvasivenessPolymerase Chain ReactionPTEN PhosphohydrolaseRac1 GTP-Binding ProteinRNA, Small InterferingStatistics, NonparametricConceptsLipid phosphatase activityPTEN-mediated inhibitionGEF activityCancer mutantsCell migrationNucleotide exchange assaysPhosphatase activityTumor suppressor PTENMouse embryonic fibroblastsTumor cell invasionPI3K pathwayHuman tumor dataKinase AktSuppressor PTENTail domainEmbryonic fibroblastsGTPase Rac1PREX2 mutationsImmortalized melanocytesMutantsCell invasionHigh PTEN expressionK pathwayRac1Breast cancer cell lines
2012
Expression of the p53 Target CDIP Correlates with Sensitivity to TNFα-Induced Apoptosis in Cancer Cells
Brown-Endres L, Schoenfeld D, Tian F, Kim HG, Namba T, Muñoz-Fontela C, Mandinova A, Aaronson SA, Lee SW. Expression of the p53 Target CDIP Correlates with Sensitivity to TNFα-Induced Apoptosis in Cancer Cells. Cancer Research 2012, 72: 2373-2382. PMID: 22549949, PMCID: PMC3349239, DOI: 10.1158/0008-5472.can-11-3369.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisApoptosis Regulatory ProteinsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansInterleukin-8MAP Kinase Kinase 4MAP Kinase Signaling SystemMiceMice, NudeNF-kappa BReactive Oxygen SpeciesRecombinant ProteinsTumor Necrosis Factor-alphaTumor Suppressor Protein p53ConceptsApoptotic cell fateCell fateCancer cellsP53-mediated deathGenotoxic stressAntiapoptotic programGrowth-suppressive effectsJNK activationApoptotic pathwaySurvival responseApoptosisDual roleExpression correlatesCellsCDIPPathwayPleiotropic cytokineFateExpressionPredictive biomarkersTNFαRegulatorDeathSurvivalActivation
2006
PECAM-1 Affects GSK-3β-Mediated β-Catenin Phosphorylation and Degradation
Biswas P, Canosa S, Schoenfeld D, Schoenfeld J, Li P, Cheas LC, Zhang J, Cordova A, Sumpio B, Madri JA. PECAM-1 Affects GSK-3β-Mediated β-Catenin Phosphorylation and Degradation. American Journal Of Pathology 2006, 169: 314-324. PMID: 16816383, PMCID: PMC1698776, DOI: 10.2353/ajpath.2006.051112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninBlotting, WesternCapillary PermeabilityCells, CulturedEndothelial CellsFluorescent Antibody TechniqueGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHistamineHistamine AgentsHumansMiceModels, BiologicalPhosphatidylinositol 3-KinasesPhosphorylationPlatelet Endothelial Cell Adhesion Molecule-1Proto-Oncogene Proteins c-aktReceptors, HistamineSignal TransductionConceptsAdherens junctionsSerine phosphorylationSrc homology 2 domainBeta-catenin expression levelsAdherens junction componentsSerine phosphorylation levelEndothelial cellsΒ-catenin phosphorylationPECAM-1Cell biological responsesCytoplasmic domainSHP-2Proteosomal degradationGSK-3betaDynamic regulatorJunction componentsPhosphorylation levelsPhosphorylationEndothelial cell adhesion molecule-1Expression levelsGSK-3βBiological responsesEndothelial barrier permeabilityMice exhibitCell adhesion molecule-1
2005
Identification of the regions of PECAM-1 involved in β- and γ-catenin associations
Biswas P, Zhang J, Schoenfeld JD, Schoenfeld D, Gratzinger D, Canosa S, Madri JA. Identification of the regions of PECAM-1 involved in β- and γ-catenin associations. Biochemical And Biophysical Research Communications 2005, 329: 1225-1233. PMID: 15766557, DOI: 10.1016/j.bbrc.2005.02.095.Peer-Reviewed Original Research
2003
PECAM-1 promotes β-catenin accumulation and stimulates endothelial cell proliferation
Biswas P, Canosa S, Schoenfeld J, Schoenfeld D, Tucker A, Madri JA. PECAM-1 promotes β-catenin accumulation and stimulates endothelial cell proliferation. Biochemical And Biophysical Research Communications 2003, 303: 212-218. PMID: 12646189, DOI: 10.1016/s0006-291x(03)00313-9.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBeta CateninBlotting, WesternCell AdhesionCell DivisionCytoplasmCytoskeletal ProteinsEndotheliumFlow CytometryHumansLungMiceMice, KnockoutMicroscopy, FluorescencePlatelet Endothelial Cell Adhesion Molecule-1Precipitin TestsSignal TransductionTrans-ActivatorsTranscription, GeneticTransfectionConceptsPECAM-1-positive endothelial cellsBeta-catenin proteinCell proliferationEndothelial cellsPECAM-1Beta-catenin localizationCytoplasmic domainΒ-catenin accumulationFull-length PECAM-1Functional consequencesEndothelial cell proliferationCell membraneKnockout animalsAdhesion moleculesLess accumulationCellsAccumulationProliferative rateProliferationMembraneProteinBinds