2020
Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions
Glitza IC, Smalley KSM, Brastianos PK, Davies MA, McCutcheon I, Liu JKC, Ahmed KA, Arrington JA, Evernden BR, Smalley I, Eroglu Z, Khushalani N, Margolin K, Kluger H, Atkins MB, Tawbi H, Boire A, Forsyth P. Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions. Pigment Cell & Melanoma Research 2020, 33: 527-541. PMID: 31916400, PMCID: PMC10126834, DOI: 10.1111/pcmr.12861.Peer-Reviewed Original ResearchMeSH KeywordsCell-Free Nucleic AcidsClinical Trials as TopicHumansMelanomaMeningeal NeoplasmsMolecular Targeted TherapyNeoplastic Cells, CirculatingConceptsLeptomeningeal diseaseMelanoma patientsCentral nervous system metastasesMelanoma Research FoundationParenchymal brain metastasesNervous system metastasesMoffitt Cancer CenterMultiple academic centersBrain metastasesCancer CenterTherapeutic managementAcademic centersClinical researchDeadly diseaseConsensus summaryDiseasePatientsMetastasisSecond summit
2019
High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling
Toki MI, Merritt CR, Wong PF, Smithy JW, Kluger HM, Syrigos KN, Ong GT, Warren SE, Beechem JM, Rimm DL. High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling. Clinical Cancer Research 2019, 25: 5503-5512. PMID: 31189645, PMCID: PMC6744974, DOI: 10.1158/1078-0432.ccr-19-0104.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyLymphocytes, Tumor-InfiltratingMaleMelanomaMolecular Diagnostic TechniquesMolecular Targeted TherapyPrognosisProportional Hazards ModelsTissue Array AnalysisTreatment OutcomeConceptsNon-small cell lung cancerProlonged progression-free survivalDigital spatial profilingOverall survivalPD-L1Predictive markerPD-L1 expressionProgression-free survivalProtein expressionCell lung cancerNovel predictive markerCD68-positive cellsStromal CD3Melanoma immunotherapyImmune markersImmune therapyPrognostic valueLung cancerAntibody cocktailTissue microarrayQuantitative fluorescenceOutcome assessmentTumor cellsHigh concordanceMultiple biomarkersMultiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma
Wong PF, Wei W, Smithy JW, Acs B, Toki MI, Blenman K, Zelterman D, Kluger HM, Rimm DL. Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma. Clinical Cancer Research 2019, 25: 2442-2449. PMID: 30617133, PMCID: PMC6467753, DOI: 10.1158/1078-0432.ccr-18-2652.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, ImmunologicalBiomarkersBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedMolecular Targeted TherapyNeoplasm StagingROC CurveT-Lymphocyte SubsetsConceptsCell countTIL activationQuantitative immunofluorescenceLymphocytic infiltrationMelanoma patientsMetastatic melanomaAnti-PD-1 responseAnti-PD-1 therapyCell death 1 (PD-1) inhibitionAbsence of immunotherapyDeath-1 (PD-1) inhibitionDisease control rateProgression-free survivalCD8 cell countsTumor-Infiltrating LymphocytesNew predictive biomarkersWhole tissue sectionsRECIST 1.1Progressive diseaseDurable responsesObjective responsePartial responseImmunotherapy outcomesLymphocyte profilesMultivariable analysisMelanoma central nervous system metastases: An update to approaches, challenges, and opportunities
Eroglu Z, Holmen SL, Chen Q, Khushalani NI, Amaravadi R, Thomas R, Ahmed KA, Tawbi H, Chandra S, Markowitz J, Smalley I, Liu JKC, Chen YA, Najjar YG, Karreth FA, Abate‐Daga D, Glitza IC, Sosman JA, Sondak VK, Bosenberg M, Herlyn M, Atkins MB, Kluger H, Margolin K, Forsyth PA, Davies MA, Smalley KSM. Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. Pigment Cell & Melanoma Research 2019, 32: 458-469. PMID: 30712316, PMCID: PMC7771318, DOI: 10.1111/pcmr.12771.Peer-Reviewed Original ResearchMeSH KeywordsCentral Nervous System NeoplasmsDisease ManagementHumansImmunotherapyMelanomaMolecular Targeted Therapy
2018
Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy
Miller NJ, Church CD, Fling SP, Kulikauskas R, Ramchurren N, Shinohara MM, Kluger HM, Bhatia S, Lundgren L, Cheever MA, Topalian SL, Nghiem P. Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy. Journal For ImmunoTherapy Of Cancer 2018, 6: 131. PMID: 30482247, PMCID: PMC6258401, DOI: 10.1186/s40425-018-0450-7.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorB-LymphocytesCarcinoma, Merkel CellHumansImmunomodulationLymphocyte ActivationMerkel cell polyomavirusMolecular Targeted TherapyPolyomavirus InfectionsProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellT-Cell Antigen Receptor SpecificityT-LymphocytesTreatment OutcomeTumor Virus InfectionsConceptsAnti-PD-1 therapyPeripheral blood mononuclear cellsB cell responsesCell responsesCell carcinomaT cellsDiverse T-cell responsePD-1 blockade therapyPre-treatment tumor biopsiesVirus-specific T cellsT-cell receptor clonalityVP-MCCCancer-specific immunityIntratumoral TCR repertoirePD-1 blockadeTumor-specific immunityT cell responsesBlood mononuclear cellsMerkel cell carcinomaAggressive skin cancerBackgroundMerkel cell carcinomaVirus-negative tumorsMerkel cell polyomavirusPresence of antigenMethodsImmune responses
2014
NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma
Giesen E, Jilaveanu LB, Parisi F, Kluger Y, Camp RL, Kluger HM. NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma. Oncotarget 2014, 5: 5209-5217. PMID: 24970819, PMCID: PMC4170640, DOI: 10.18632/oncotarget.2101.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmCarcinoma, Renal CellCohort StudiesHumansImmunotherapyKidney NeoplasmsMembrane ProteinsMolecular Targeted TherapyNeoplasm MetastasisTissue Array AnalysisConceptsNY-ESO-1 expressionNY-ESO-1Renal cell carcinomaCell carcinomaMetastatic sitesRenal tissueCancer-testis antigen NY-ESO-1Antigen NY-ESO-1Adjacent normal renal tissuesClear cell renal cell carcinomaRCC specimensMetastatic RCC specimensPapillary renal cell carcinomaCell renal cell carcinomaPotential immunotherapeutic targetAdoptive cell therapySubset of RCCTumor-specific antigensClear cell carcinomaNovel immune therapiesPrimary RCC specimensBenign renal tissueNormal renal tissueDifferent tumor sitesImmune therapy
2013
Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel
Jilaveanu LB, Zhao F, Zito CR, Kirkwood JM, Nathanson KL, D'Andrea K, Wilson M, Rimm DL, Flaherty KT, Lee SJ, Kluger HM. Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel. PLOS ONE 2013, 8: e69748. PMID: 23936348, PMCID: PMC3735539, DOI: 10.1371/journal.pone.0069748.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalVEGF-R1FGF-R1Paclitaxel-based therapyVEGF-R1 expressionPre-treatment tumorsPredictive biomarker signaturesMultitarget kinase inhibitorPDGF-RβSitu protein expressionTherapeutic ratioTaxane sensitivityMitogen-activated protein kinase pathwayPatientsVEGF-R3CarboplatinSorafenibVEGF-R2C-kitKinase inhibitorsTherapyProtein expressionPhase IIISorafenib targets
2012
Chapter One Vertical Pathway Targeting in Cancer Therapy
Shahbazian D, Sznol J, Kluger HM. Chapter One Vertical Pathway Targeting in Cancer Therapy. Advances In Pharmacology 2012, 65: 1-26. PMID: 22959021, DOI: 10.1016/b978-0-12-397927-8.00001-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsHumansMitogensMolecular Targeted TherapyNeoplasmsOncogenesSignal TransductionConceptsVital cellular processesDifferent signaling pathwaysDNA maintenanceCellular processesCell divisionDrug combinationsSignaling pathwaysSame pathwayAdaptive responseParticular mutationCell proliferationRecent discoveryPathwayTypes of cancerFragile nodesAdditional targetsGrowth inhibitoryUnavoidable toxicitiesMutationsMultitarget inhibitionCytotoxic effectsCancer researchSolid tumorsProlonged responseMalignant cells
2011
Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer
Elfiky AA, Aziz SA, Conrad PJ, Siddiqui S, Hackl W, Maira M, Robert CL, Kluger HM. Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer. Journal Of Translational Medicine 2011, 9: 133. PMID: 21834980, PMCID: PMC3173341, DOI: 10.1186/1479-5876-9-133.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisAutomationBiomarkers, TumorCarcinoma, Renal CellCell Line, TumorChromonesDrug SynergismHumansImidazolesInhibitory Concentration 50Kidney NeoplasmsMolecular Targeted TherapyMorpholinesMultivariate AnalysisPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsQuinolinesSirolimusTOR Serine-Threonine KinasesConceptsRenal cell carcinomaRCC cell linesNVP-BEZ235PI3KMTOR expressionMetastatic renal cell carcinomaPI3K subunitsHigh mTOR expressionAutomated Quantitative AnalysisRCC cell growthRenal cell cancerExpression of p85PI3K inhibitor LY294002Cell linesWarrants further investigationK inhibitor LY294002PI3K inhibitorsMulti-variable analysisCell cancerCell carcinomaClinical trialsSitu protein expressionNephrectomy casesTissue microarrayMTOR inhibitors
2010
Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma
Aziz SA, Jilaveanu LB, Zito C, Camp RL, Rimm DL, Conrad P, Kluger HM. Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma. Clinical Cancer Research 2010, 16: 6029-6039. PMID: 21169255, PMCID: PMC3058635, DOI: 10.1158/1078-0432.ccr-10-1490.Peer-Reviewed Original Research