2022
Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma
Oria VO, Zhang H, Zito CR, Rane CK, Ma XY, Provance OK, Tran TT, Adeniran A, Kluger Y, Sznol M, Bosenberg MW, Kluger HM, Jilaveanu LB. Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma. Cellular And Molecular Life Sciences 2022, 79: 377. PMID: 35737114, PMCID: PMC9226089, DOI: 10.1007/s00018-022-04364-5.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsFibromodulinHumansMelanomaNeoplasm MetastasisSignal TransductionSOXB1 Transcription FactorsTranscription FactorsConceptsTumor suppressor Hippo pathwayNovel regulatory mechanismTumor vasculogenic mimicryMetastatic outgrowthExtracellular matrix componentsHippo pathwayRegulatory mechanismsMolecular eventsTumor-stroma interactionsCritical regulatorMetastatic competenceProgenitor markersProliferative stateFunctional roleFunctional studiesSOX2Vasculogenic mimicryDistinct phenotypesMatrix componentsEarly developmentFmodHigh expressionCritical processOutgrowthImportant role
2020
Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design
Khushalani NI, Diab A, Ascierto PA, Larkin J, Sandhu S, Sznol M, Koon HB, Jarkowski A, Zhou M, Statkevich P, Geese WJ, Long GV. Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design. Future Oncology 2020, 16: 2165-2175. PMID: 32723187, DOI: 10.2217/fon-2020-0351.Peer-Reviewed Original ResearchConceptsMetastatic melanomaKey secondary end pointEnd pointSafety/tolerabilityObjective response ratePD-1 inhibitorsPrimary end pointSecondary end pointsFirst-line therapyProgression-free survivalNatural killer cellsOverall survivalSurvival benefitAdvanced melanomaKiller cellsClinical trialsEffector TClinical activityNivolumabBempegaldesleukinResponse rateMelanomaPathway agonistStudy designPhase IIIReversing Resistance to Checkpoint Inhibitors and Targeted Therapy in Metastatic Melanoma.
Sznol M. Reversing Resistance to Checkpoint Inhibitors and Targeted Therapy in Metastatic Melanoma. Clinical Advances In Hematology And Oncology 2020, 18: 408-410. PMID: 32903252.Peer-Reviewed Original ResearchSurvival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma
Klemen ND, Wang M, Rubinstein JC, Olino K, Clune J, Ariyan S, Cha C, Weiss SA, Kluger HM, Sznol M. Survival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma. Journal For ImmunoTherapy Of Cancer 2020, 8: e000341. PMID: 32209601, PMCID: PMC7103823, DOI: 10.1136/jitc-2019-000341.Peer-Reviewed Original ResearchMeSH KeywordsAgedFemaleHumansMaleMelanomaMiddle AgedNeoplasm MetastasisSkin NeoplasmsSurvival AnalysisUveal NeoplasmsConceptsCheckpoint inhibitorsOverall survivalMetastatic melanomaPrimary tumorLocal therapyCutaneous melanomaAnti-PD-1 antibodyAggressive multidisciplinary approachCutaneous primary tumorPrimary tumor histologyMedian overall survivalSingle institutional experienceRare melanoma subtypeMedian OSMetastatic diseaseProgressive diseaseAcral skinComplete responsePD-1PD-L1Uveal tractTumor histologyCombination therapyCTLA-4Longer survival
2019
Immunotherapy of Melanoma: Facts and Hopes
Weiss SA, Wolchok JD, Sznol M. Immunotherapy of Melanoma: Facts and Hopes. Clinical Cancer Research 2019, 25: 5191-5201. PMID: 30923036, PMCID: PMC6726509, DOI: 10.1158/1078-0432.ccr-18-1550.Peer-Reviewed Original ResearchConceptsOverall survivalMetastatic diseaseImmune therapyPredictive biomarkersNivolumab/ipilimumab combinationRandomized phase III trialLong-term clinical benefitImmunobiology of tumorsDuration of therapyPhase III trialsLong-term survivorsEffective immune therapyAdjuvant settingIpilimumab combinationMetastatic settingIII trialsPatient subsetsClinical benefitImmune modulationMetastatic melanomaClinical trialsSingle agentTherapyTrue increaseCell therapy
2018
A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma
Weber JS, Sznol M, Sullivan RJ, Blackmon S, Boland G, Kluger HM, Halaban R, Bacchiocchi A, Ascierto PA, Capone M, Oliveira C, Meyer K, Grigorieva J, Asmellash SG, Roder J, Roder H. A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma. Cancer Immunology Research 2018, 6: 79-86. PMID: 29208646, DOI: 10.1158/2326-6066.cir-17-0412.Peer-Reviewed Original ResearchConceptsAcute phase reactantsCheckpoint inhibitorsOverall survivalPhase reactantsIpilimumab-treated patientsPD-1 blockadeTrials of nivolumabBetter overall survivalIndependent patient cohortsPretreatment serumPD-1Melanoma patientsValidation cohortMetastatic melanomaMultipeptide vaccinePatient cohortPooled analysisWorse outcomesClinical dataPatientsMultivariate analysisComplement cascadeMass spectrometry analysisNivolumabCohort
2017
The Phoenix Rises: The Rebirth of Cancer Immunotherapy
Blasutig IM, Farkona S, Buchbinder EI, Luke JJ, Sharma P, Sznol M. The Phoenix Rises: The Rebirth of Cancer Immunotherapy. Clinical Chemistry 2017, 63: 1190-1195. PMID: 28515097, DOI: 10.1373/clinchem.2016.267849.Peer-Reviewed Original ResearchNuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma
Smithy JW, Moore LM, Pelekanou V, Rehman J, Gaule P, Wong PF, Neumeister VM, Sznol M, Kluger HM, Rimm DL. Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2017, 5: 25. PMID: 28331615, PMCID: PMC5359951, DOI: 10.1186/s40425-017-0229-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, PharmacologicalDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyInterferon Regulatory Factor-1IpilimumabMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasms, Second PrimaryNivolumabProgrammed Cell Death 1 ReceptorConceptsProgression-free survivalObjective radiographic responsePD-L1 expressionPD-L1IRF-1 expressionMetastatic melanomaAnti-PD-1 therapyCombination ipilimumab/nivolumabHigh PD-L1 expressionAnti-PD-1 immunotherapyYale-New Haven HospitalIpilimumab/nivolumabPD-1 therapyPR/CRPre-treatment formalinRECIST v1.1 criteriaDeath ligand 1Valuable predictive biomarkerMajor unmet needNew Haven HospitalInterferon regulatory factor 1Combination ipilimumabProgressive diseaseRadiographic responseComplete response
2015
Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer
Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, Sequist LV, Smith DC, Leming P, Carbone DP, Pinder-Schenck MC, Topalian SL, Hodi FS, Sosman JA, Sznol M, McDermott DF, Pardoll DM, Sankar V, Ahlers CM, Salvati M, Wigginton JM, Hellmann MD, Kollia GD, Gupta AK, Brahmer JR. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2015, 33: 2004-2012. PMID: 25897158, PMCID: PMC4672027, DOI: 10.1200/jco.2014.58.3708.Peer-Reviewed Original ResearchConceptsOverall survivalLong-term safetyAdvanced NSCLCLung cancerDeath-1 immune checkpoint inhibitor antibodyAdvanced non-small cell lung cancerNon-small cell lung cancerImmune checkpoint inhibitor antibodyTreatment-related adverse eventsCheckpoint inhibitor antibodyTreatment-related deathsMedian overall survivalMedian response durationAdvanced solid tumorsPhase I trialCell lung cancerRandomized clinical trialsFurther clinical developmentHuman immunoglobulin G4Nivolumab 1Nivolumab monotherapyExpansion cohortLast doseNonsquamous NSCLCAdverse events
2012
Chitinase-like Proteins in Lung Injury, Repair, and Metastasis
Lee CG, Dela Cruz CS, Ma B, Ahangari F, Zhou Y, Halaban R, Sznol M, Elias JA. Chitinase-like Proteins in Lung Injury, Repair, and Metastasis. Annals Of The American Thoracic Society 2012, 9: 57-61. PMID: 22550243, PMCID: PMC3359113, DOI: 10.1513/pats.201112-056ms.Peer-Reviewed Original Research
2011
Plasma Markers for Identifying Patients with Metastatic Melanoma
Kluger HM, Hoyt K, Bacchiocchi A, Mayer T, Kirsch J, Kluger Y, Sznol M, Ariyan S, Molinaro A, Halaban R. Plasma Markers for Identifying Patients with Metastatic Melanoma. Clinical Cancer Research 2011, 17: 2417-2425. PMID: 21487066, PMCID: PMC3415234, DOI: 10.1158/1078-0432.ccr-10-2402.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntigens, CDBiomarkers, TumorCell Adhesion MoleculesEnzyme-Linked Immunosorbent AssayExtracellular Matrix ProteinsFemaleGlycoproteinsGrowth Differentiation Factor 15HumansIntercellular Adhesion Molecule-1L-Lactate DehydrogenaseMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasm ProteinsNeoplasm Recurrence, LocalNeoplasm StagingNerve Growth FactorsPrognosisReproducibility of ResultsS100 Calcium Binding Protein beta SubunitS100 ProteinsSensitivity and SpecificityTissue Inhibitor of Metalloproteinase-1ConceptsGenome-wide gene expression dataGene expression dataHigh expression levelsLevels of proteinExpression dataExpression levelsProteinMelanoma cellsStage I/II diseaseEqual-sized trainingMarkersGenesDisease recurrencePlasma markersMetastatic melanomaTIMP-1Lactate dehydrogenaseCEACAMsStage I/II patientsDehydrogenaseOsteopontinStage IV diseaseStage IV patientsMetastatic melanoma patientsGender-matched patients
2010
A phase 2 trial of dasatinib in advanced melanoma
Kluger HM, Dudek AZ, McCann C, Ritacco J, Southard N, Jilaveanu LB, Molinaro A, Sznol M. A phase 2 trial of dasatinib in advanced melanoma. Cancer 2010, 117: 2202-2208. PMID: 21523734, PMCID: PMC3116034, DOI: 10.1002/cncr.25766.Peer-Reviewed Original ResearchConceptsProgression-free survivalC-kit mutationsPhase 2 trialResponse ratePartial responseMedian progression-free survivalMelanoma cell proliferationDaily dasatinibMucosal primaryPFS ratesStarting dosageCommon toxicitiesUnresectable melanomaAdvanced melanomaPleural effusionMelanoma patientsPredictive biomarkersMinor responseCombination trialsTumor assessmentDose reductionPatientsPrespecified endpointsDasatinibMelanoma
2007
The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization
Kluger HM, McCarthy MM, Alvero AB, Sznol M, Ariyan S, Camp RL, Rimm DL, Mor G. The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization. Journal Of Translational Medicine 2007, 5: 6. PMID: 17257402, PMCID: PMC1796544, DOI: 10.1186/1479-5876-5-6.Peer-Reviewed Original ResearchConceptsMetastatic melanomaXIAP expressionCell linesCy5-conjugated antibodiesMechanism of actionMelanoma cell linesPrimary lesionOvarian cancerTherapeutic approachesTissue microarrayDisease aggressionCarboplatin sensitivityChemotherapy resistanceMalignant progressionClinical specimensBenign counterpartsCarboplatinMelanomaChemotherapy sensitizationPrimary specimensPhenoxodiolResistant cellsMelanoma cellsHigh expressionMelanoma resistance
2006
Expression of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Receptors 1 and 2 in Melanoma
McCarthy MM, DiVito KA, Sznol M, Kovacs D, Halaban R, Berger AJ, Flaherty KT, Camp RL, Lazova R, Rimm DL, Kluger HM. Expression of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Receptors 1 and 2 in Melanoma. Clinical Cancer Research 2006, 12: 3856-3863. PMID: 16778114, PMCID: PMC1839847, DOI: 10.1158/1078-0432.ccr-06-0190.Peer-Reviewed Original Research