2020
Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases
Weiss SA, Zito C, Tran T, Heishima K, Neumeister V, McGuire J, Adeniran A, Kluger H, Jilaveanu LB. Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases. Journal Of Neuro-Oncology 2020, 152: 15-25. PMID: 32974852, PMCID: PMC7910371, DOI: 10.1007/s11060-020-03619-0.Peer-Reviewed Original ResearchConceptsT-cell contentMelanoma brain metastasesPD-L1 expressionLower microvessel densityMicrovessel densityBrain metastasesExtracranial metastasesMacrophage contentB cellsProspective therapeutic clinical trialsTumor-infiltrating T cellsImmune-modulating drugsImmune cell subsetsTherapeutic clinical trialsExtracerebral metastasesHigh CD68Low CD3Low CD8Systemic therapyIntracerebral metastasesMetastatic sitesCell subsetsMetastatic melanomaImmune cellsClinical trials19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA
Oria V, Zhang H, Zhu H, Deng G, Zito C, Rane C, Zhang S, Weiss S, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg M, Kluger H, Jilaveanu L. 19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA. Neuro-Oncology Advances 2020, 2: ii3-ii3. PMCID: PMC7401364, DOI: 10.1093/noajnl/vdaa073.009.Peer-Reviewed Original ResearchMelanoma brain metastasesBrain metastasesTumor growthPI3K/Akt/mTORCell cycle transitionAkt/mTORGrowth of tumorsS cell cycle transitionPhosphorylation of AktMelanoma patientsPoor prognosisNovel drug targetsPatient populationRegulation of PDCD4Metastatic melanomaUnique cohortXenograft modelClinical relevanceNude miceMetastasisCycle transitionMelanomaBrain developmentKey mediatorMelanoma cellsSystemic Therapy for Brain Metastases: Melanoma
Weiss S, Kluger H. Systemic Therapy for Brain Metastases: Melanoma. 2020, 235-244. DOI: 10.1007/978-3-030-42958-4_16.Peer-Reviewed Original ResearchMelanoma brain metastasesIntracranial response ratesBrain metastasesClinical trialsResponse rateAnti-PD-1 monotherapyCentral nervous system metastasesExtracranial metastatic sitesNervous system metastasesSystemic therapy approachesMultiple clinical trialsSystemic therapySystemic treatmentAdvanced melanomaImmune checkpointsMetastatic sitesTherapeutic challengePatient survivalMetastatic melanomaExtracranial sitesStereotactic radiosurgeryMetastasisMutant BRAFSignificant causeMEK inhibition
2019
PLEKHA5 regulates tumor growth in metastatic melanoma
Zhang H, Zhu H, Deng G, Zito CR, Oria VO, Rane CK, Zhang S, Weiss SA, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg MW, Kluger HM, Jilaveanu LB. PLEKHA5 regulates tumor growth in metastatic melanoma. Cancer 2019, 126: 1016-1030. PMID: 31769872, PMCID: PMC7147081, DOI: 10.1002/cncr.32611.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsApoptosis Regulatory ProteinsBiomarkers, TumorBrain NeoplasmsCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMaleMelanomaMiceMice, NudeMiddle AgedPhosphatidylinositol 3-KinasesPrognosisProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesTumor Cells, CulturedXenograft Model Antitumor AssaysYoung AdultConceptsTumor growthDisseminated melanomaExtracranial melanoma metastasesPI3K/AKT/mTOR pathwayMelanoma brain metastasesBetter overall survivalPI3K/Akt/mTORAKT/mTOR pathwayCell proliferationAkt/mTORMelanoma xenograft modelGrowth of tumorsS cell cycle transitionBrain metastasesOverall survivalPoor prognosisMetastatic melanomaMAPK/ERKSubcutaneous inoculationMelanoma metastasesXenograft modelClinical relevanceMelanoma growthNude miceCerebral specimens
2018
Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial
Kluger HM, Chiang V, Mahajan A, Zito CR, Sznol M, Tran T, Weiss SA, Cohen JV, Yu J, Hegde U, Perrotti E, Anderson G, Ralabate A, Kluger Y, Wei W, Goldberg SB, Jilaveanu LB. Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. Journal Of Clinical Oncology 2018, 37: 52-60. PMID: 30407895, PMCID: PMC6354772, DOI: 10.1200/jco.18.00204.Peer-Reviewed Original ResearchConceptsBrain metastasis responseBrain metastasesMetastasis responseAdverse eventsAnti-programmed cell death-1 (PD-1) agentsDeath ligand 1 (PD-L1) expressionModified Response Evaluation CriteriaPhase II clinical trialActive brain metastasesAsymptomatic brain metastasesCD8 cell densityNeurologic adverse eventsPembrolizumab-treated patientsUse of pembrolizumabMelanoma brain metastasesPrimary end pointLigand 1 expressionPhase II trialResponse Evaluation CriteriaT-cell infiltratesUntreated brain metastasesDeath ligand 1Two-year survivalOverall survival timeResult of progression
2016
Melanoma brain metastases: correlation of imaging features with genomic markers and patient survival
Bordia R, Zhong H, Lee J, Weiss S, Han SW, Osman I, Jain R. Melanoma brain metastases: correlation of imaging features with genomic markers and patient survival. Journal Of Neuro-Oncology 2016, 131: 341-348. PMID: 27822597, DOI: 10.1007/s11060-016-2305-8.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesSignificant prognostic factorsBRAF inhibitor treatmentPercent of lesionsBrain metastasesMedian survivalPrognostic factorsPatient survivalMultiple lesionsInhibitor treatmentT1-weighted hyperintensityBRAF mutation statusT1-weighted hyperintense signalsNumber of lesionsMethods PatientsRetrospective reviewInstitutional databaseLonger survivalHyperintense signalBrain MRIMelanoma metastasesSingle lesionEnhancement patternLarge lesionsLesion size
2015
Somatic and germline analyses of a long term melanoma survivor with a recurrent brain metastasis
Weiss S, Darvishian F, Tadepalli J, Shapiro R, Golfinos J, Pavlick A, Polsky D, Kirchhoff T, Osman I. Somatic and germline analyses of a long term melanoma survivor with a recurrent brain metastasis. BMC Cancer 2015, 15: 926. PMID: 26597176, PMCID: PMC4657192, DOI: 10.1186/s12885-015-1927-0.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesRecurrent brain metastasesBrain metastasesOverall survivalLong-term melanoma survivorsSingle nucleotide polymorphismsYear old manIndividual patient's tumorGenetic variantsMelanoma patientsMelanoma survivorsPrognostic informationFavorable outcomeNRAS wild typePatient outcomesConclusionsOur dataPatient tumorsImmune functionBrain tumorsExtended survivalOlder menPatientsClinical scenariosGermline analysisTherapeutic interventionsDabrafenib for the treatment of melanoma
Weiss S, Pavlick A. Dabrafenib for the treatment of melanoma. Expert Opinion On Orphan Drugs 2015, 3: 1075-1084. DOI: 10.1517/21678707.2015.1067136.Peer-Reviewed Original ResearchAdvanced melanomaBrain metastasesBRAF V600EEffective salvage therapyMilestone clinical trialsPractice-changing approachAdvanced melanoma patientsHigh tumor burdenMelanoma brain metastasesFirst-line therapyMajority of patientsMEK inhibitor trametinibBRAF inhibitor therapyTreatment of melanomaV600K mutationsMutant BRAF kinaseMechanism of actionSalvage therapyAdverse eventsInhibitor therapyMelanoma patientsTumor burdenPoor prognosisCancer symptomsIL-2