2023
Epigenomic charting and functional annotation of risk loci in renal cell carcinoma
Nassar A, Abou Alaiwi S, Baca S, Adib E, Corona R, Seo J, Fonseca M, Spisak S, El Zarif T, Tisza V, Braun D, Du H, He M, Flaifel A, Alchoueiry M, Denize T, Matar S, Acosta A, Shukla S, Hou Y, Steinharter J, Bouchard G, Berchuck J, O’Connor E, Bell C, Nuzzo P, Mary Lee G, Signoretti S, Hirsch M, Pomerantz M, Henske E, Gusev A, Lawrenson K, Choueiri T, Kwiatkowski D, Freedman M. Epigenomic charting and functional annotation of risk loci in renal cell carcinoma. Nature Communications 2023, 14: 346. PMID: 36681680, PMCID: PMC9867739, DOI: 10.1038/s41467-023-35833-5.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Renal CellEpigenomicsForkhead Transcription FactorsHumansKidney NeoplasmsOncogenesTranscription FactorsConceptsMaster transcription factorChIP-seqATAC-seq dataH3K27ac ChIP-seqCcRCC cell linesEpigenomic atlasATAC-seqFunctional annotationTranscriptional landscapePrimary human samplesTranscription factorsRNA-seqRisk lociTranscriptional upregulationSNP arrayRisk SNPsETS-1EpigenomeCell linesFOXI1Renal cell carcinomaEPAS1RCC histologic subtypesHuman samplesBHLHE41
2021
Gene Expression Signature Correlates with Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Everolimus Alone or with a Vascular Disrupting Agent
Yang ES, Nassar AH, Adib E, Jegede OA, Alaiwi SA, Manna DLD, Braun DA, Zarei M, Du H, Pal SK, Naik G, Sonpavde GP. Gene Expression Signature Correlates with Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Everolimus Alone or with a Vascular Disrupting Agent. Molecular Cancer Therapeutics 2021, 20: 1454-1461. PMID: 34108261, DOI: 10.1158/1535-7163.mct-20-1091.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBenzofuransBiomarkers, TumorCarcinoma, Renal CellClinical Trials, Phase III as TopicEverolimusFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansKidney NeoplasmsMaleMiddle AgedOrganophosphatesPrognosisSurvival RateTranscriptomeValidation Studies as TopicConceptsMetastatic renal cell carcinomaMedian PFSClinical benefitDiscovery cohortMetastatic renal cell carcinoma patientsPhase I/II trialRenal cell carcinoma patientsPhase III trialsCell carcinoma patientsLonger median PFSRenal cell carcinomaFour-gene signaturePropensity score covariate adjustmentVascular Disrupting AgentsCheckMate 025Monotherapy useStable diseaseII trialGene expression signaturesIII trialsAppropriate patientsCarcinoma patientsImmune checkpointsCell carcinomaVEGF inhibitorsIntegrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Bakouny Z, Braun DA, Shukla SA, Pan W, Gao X, Hou Y, Flaifel A, Tang S, Bosma-Moody A, He MX, Vokes N, Nyman J, Xie W, Nassar AH, Abou Alaiwi S, Flippot R, Bouchard G, Steinharter JA, Nuzzo PV, Ficial M, Sant’Angelo M, Forman J, Berchuck JE, Dudani S, Bi K, Park J, Camp S, Sticco-Ivins M, Hirsch L, Baca SC, Wind-Rotolo M, Ross-Macdonald P, Sun M, Lee GM, Chang SL, Wei XX, McGregor BA, Harshman LC, Genovese G, Ellis L, Pomerantz M, Hirsch MS, Freedman ML, Atkins MB, Wu CJ, Ho TH, Linehan WM, McDermott DF, Heng DYC, Viswanathan SR, Signoretti S, Van Allen EM, Choueiri TK. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nature Communications 2021, 12: 808. PMID: 33547292, PMCID: PMC7865061, DOI: 10.1038/s41467-021-21068-9.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalB7-H1 AntigenCarcinoma, Renal CellCTLA-4 AntigenCyclin-Dependent Kinase Inhibitor p16Gene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansImmune Checkpoint InhibitorsImmune Checkpoint ProteinsKidney NeoplasmsMutationProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-mycRetrospective StudiesRhabdoid TumorSignal TransductionSurvival AnalysisTranscription, GeneticTumor Suppressor ProteinsUbiquitin ThiolesteraseConceptsRhabdoid renal cell carcinomaImmune checkpoint inhibitorsRenal cell carcinomaCell carcinomaImmune-inflamed phenotypeIntegrative molecular characterizationPD-L1 expressionReal-world cohortMultiple clinical trialsMYC transcriptional programsMolecular featuresCheckpoint inhibitorsClinical outcomesImmune activationImmunologic characteristicsAggressive tumorsImmune infiltrationClinical trialsClinical characterizationRCC tumorsBAP1 mutationsDistinctive molecular featuresTumorsCDKN2A deletionMolecular drivers
2020
Activity of cabozantinib after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma
McGregor BA, Lalani AA, Xie W, Steinharter JA, Bakouny Z, Martini DJ, Fleischer JH, Abou-Alaiwi S, Nassar A, Nuzzo PV, Kaymakcalan MD, Braun DA, Wei XX, Harshman LC, Bilen MA, Choueiri TK. Activity of cabozantinib after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma. European Journal Of Cancer 2020, 135: 203-210. PMID: 32599410, DOI: 10.1016/j.ejca.2020.05.009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiogenesis InhibitorsAnilidesAntineoplastic Combined Chemotherapy ProtocolsBostonCarcinoma, Renal CellFemaleGeorgiaHumansImmune Checkpoint InhibitorsKidney NeoplasmsMaleMiddle AgedProtein Kinase InhibitorsPyridinesRetrospective StudiesTime FactorsTreatment OutcomeConceptsMetastatic clear cell renal cell carcinomaImmune checkpoint blockadeClear cell renal cell carcinomaActivity of cabozantinibRenal cell carcinomaOverall survivalTreatment failureCheckpoint blockadeCell carcinomaDose reductionAnti-PD-1/PD-L1International Metastatic RCC Database ConsortiumVascular endothelial growth factor inhibitorsSubsequent-line treatmentUse of cabozantinibIntermediate-risk groupMedian overall survivalMedian TTFHalf of patientsNew safety signalsPalmar-plantar erythrodysesthesiaPrimary progressive diseaseGrowth factor inhibitorsOverall response rateMost common reasonsPlasma cell-free DNA variant analysis compared with methylated DNA analysis in renal cell carcinoma
Lasseter K, Nassar AH, Hamieh L, Berchuck JE, Nuzzo PV, Korthauer K, Shinagare AB, Ogorek B, McKay R, Thorner AR, Lee GM, Braun DA, Bhatt RS, Freedman M, Choueiri TK, Kwiatkowski DJ. Plasma cell-free DNA variant analysis compared with methylated DNA analysis in renal cell carcinoma. Genetics In Medicine 2020, 22: 1366-1373. PMID: 32341571, DOI: 10.1038/s41436-020-0801-x.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCarcinoma, Renal CellCell-Free Nucleic AcidsDNAHigh-Throughput Nucleotide SequencingHumansKidney NeoplasmsPlasmaConceptsMRCC patientsCancer subtypesCfDNA analysisMetastatic RCC patientsRenal cell carcinomaMRCC casesRCC patientsCell carcinomaControl subjectsVariant analysisCfDNA variantsSeparate cohortPatientsSerial samplesGermline variantsTumor sequencingClonal hematopoiesisVariant findingsTherapyCandidate variantsSubtypesCancer detectionCfMeDIP-seqVariant frequencyCarcinoma
2019
PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN
Flaifel A, Xie W, Braun DA, Ficial M, Bakouny Z, Nassar AH, Jennings RB, Escudier B, George DJ, Motzer RJ, Morris MJ, Powles T, Wang E, Huang Y, Freeman GJ, Choueiri TK, Signoretti S. PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN. Clinical Cancer Research 2019, 25: 6080-6088. PMID: 31371341, PMCID: PMC6801080, DOI: 10.1158/1078-0432.ccr-19-1135.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnilidesB7-H1 AntigenBiomarkers, TumorBiopsyCarcinoma, Renal CellChemotherapy, AdjuvantClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicEverolimusFemaleHumansKaplan-Meier EstimateKidneyKidney NeoplasmsMulticenter Studies as TopicNephrectomyPrognosisProgression-Free SurvivalProtein Kinase InhibitorsPyridinesRandomized Controlled Trials as TopicSunitinibConceptsMetastatic renal cell carcinomaPD-L1 expressionProgression-free survivalOverall survivalRenal cell carcinomaPD-L1Clinical outcomesCell carcinomaPredictive biomarkersClinical trialsTumor cell PD-L1 expressionHigh PD-L1 expressionTC PD-L1 expressionImproved progression-free survivalTumor tissuePoor progression-free survivalIHC double stainingMET expression levelsImmune cell infiltratesPD-L1 statusWorse clinical outcomesPotential predictive biomarkersImmune cell densityIndependent central reviewCABOSUN trial