2021
A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial response
2020
Regulation of eIF2α by RNF4 Promotes Melanoma Tumorigenesis and Therapy Resistance
Avitan-Hersh E, Feng Y, Oknin Vaisman A, Abu Ahmad Y, Zohar Y, Zhang T, Lee JS, Lazar I, Sheikh Khalil S, Feiler Y, Kluger H, Kahana C, Brown K, Ruppin E, Ronai ZA, Orian A. Regulation of eIF2α by RNF4 Promotes Melanoma Tumorigenesis and Therapy Resistance. Journal Of Investigative Dermatology 2020, 140: 2466-2477. PMID: 32360601, PMCID: PMC8081033, DOI: 10.1016/j.jid.2020.04.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell Line, TumorDrug Resistance, NeoplasmEukaryotic Initiation Factor-2FemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMelanomaMiceMitogen-Activated Protein KinasesNuclear ProteinsOncogenesPrognosisProtein Kinase InhibitorsProtein StabilityProto-Oncogene Proteins B-rafSkinSkin NeoplasmsTranscription FactorsUbiquitinationXenograft Model Antitumor AssaysConceptsUbiquitin ligase RNF4Elongation factor alphaPatient-derived melanomasIntegrated stress responseTherapy resistancePositive feed-forward loopTranscription factor 4Feed-forward loopOncogenic translationMolecular machineryMajor clinical challengePhosphorylated eIF2αHallmark of melanomaXenograft mouse modelHomologous proteinsStress responseMAPK inhibitorProtein stabilizationMelanoma tumorigenesisTumorigenic propertiesPoor prognosisFactor alphaClinical challengeMouse modelRNF4
2017
Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States
Gangadhar TC, Hwu WJ, Postow MA, Hamid O, Daud A, Dronca R, Joseph R, O’Day S, Hodi FS, Pavlick AC, Kluger H, Oxborough RP, Yang A, Gazdoiu M, Kush DA, Ebbinghaus S, Salama AKS. Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States. Journal Of Immunotherapy 2017, 40: 334-340. PMID: 29028788, PMCID: PMC5647109, DOI: 10.1097/cji.0000000000000186.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsClinical Trials as TopicDrug Resistance, NeoplasmDrug-Related Side Effects and Adverse ReactionsExanthemaFatigueFemaleHumansMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasm StagingTreatment OutcomeUnited StatesYoung AdultConceptsTreatment-related adverse eventsAdverse eventsAdvanced melanomaGrade 3/4 treatment-related adverse eventsNational Cancer Institute Common Terminology CriteriaUnresectable stage III/IV melanomaStage III/IV melanomaImmune-related response criteriaDeath-1 antibodySafety of pembrolizumabTreatment-related deathsUse of pembrolizumabCommon Terminology CriteriaObjective response rateSubcutaneous tissue disordersAccess programEvaluable patientsTerminology CriteriaCare therapyComplete responseInvestigator reviewGastrointestinal disordersDisease progressionTissue disordersBRAF inhibitors
2015
Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas
Krauthammer M, Kong Y, Bacchiocchi A, Evans P, Pornputtapong N, Wu C, McCusker JP, Ma S, Cheng E, Straub R, Serin M, Bosenberg M, Ariyan S, Narayan D, Sznol M, Kluger HM, Mane S, Schlessinger J, Lifton RP, Halaban R. Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas. Nature Genetics 2015, 47: 996-1002. PMID: 26214590, PMCID: PMC4916843, DOI: 10.1038/ng.3361.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBenzimidazolesDNA Mutational AnalysisDrug Resistance, NeoplasmExomeGenetic Association StudiesGenetic Predisposition to DiseaseHumansInhibitory Concentration 50Kaplan-Meier EstimateLoss of HeterozygosityMaleMelanomaMutation, MissenseNeurofibromin 1Ras ProteinsSequence Analysis, RNASkin NeoplasmsSunlightTumor Cells, Cultured
2011
In vitro studies of dasatinib, its targets and predictors of sensitivity
Jilaveanu LB, Zito CR, Aziz SA, Chakraborty A, Davies MA, Camp RL, Rimm DL, Dudek A, Sznol M, Kluger HM. In vitro studies of dasatinib, its targets and predictors of sensitivity. Pigment Cell & Melanoma Research 2011, 24: 386-389. PMID: 21320292, PMCID: PMC4431976, DOI: 10.1111/j.1755-148x.2011.00835.x.Peer-Reviewed Original Research
2008
Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer
Nadler Y, Camp RL, Giltnane JM, Moeder C, Rimm DL, Kluger HM, Kluger Y. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Research 2008, 10: r35. PMID: 18430249, PMCID: PMC2397537, DOI: 10.1186/bcr1998.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsDNA-Binding ProteinsDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateLymphatic MetastasisMiddle AgedPredictive Value of TestsPrognosisProportional Hazards ModelsProtein Array AnalysisProto-Oncogene Proteins c-bcl-2Receptors, EstrogenReceptors, ProgesteroneTranscription FactorsTreatment OutcomeConceptsNode-positive subsetHER2/neuProgesterone receptorBreast cancerEstrogen receptorBcl-2 expressionBAG-1 expressionImproved survivalBcl-2Anti-apoptotic mediator Bcl-2Breast tumorsSteroid receptor positivitySubset of patientsBAG-1Antihormonal therapyFavorable prognosisReceptor positivityMultivariable analysisPathological variablesEntire cohortPrognostic valuePrognostic markerImproved outcomesLarge cohortClinical development