2024
NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion
Noronha K, Lucas K, Paradkar S, Edmonds J, Friedman S, Murray M, Liu S, Sajed D, Sachs C, Spurrier J, Raponi M, Liang J, Zeng H, Sundaram R, Shuch B, Vasquez J, Bindra R. NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion. Molecular Cancer Research 2024, 22: of1-of16. PMID: 38949523, PMCID: PMC11445649, DOI: 10.1158/1541-7786.mcr-23-1003.Peer-Reviewed Original ResearchRenal cell carcinomaCellular processesCell carcinomaFumarate hydrataseImpact diverse cellular processesAlpha-ketoglutarate-dependent dioxygenasesDiverse cellular processesAccumulation of fumaratePreiss-Handler pathwayMultiple cellular processesLoss of function mutationsAssociated with silencingNicotinamide phosphoribosyl transferase inhibitorPattern of hypermethylationFH-deficient renal cell carcinomasSynergistic tumor cell killingAggressive subtype of renal cell carcinomaLoss of FHSubtype of renal cell carcinomaDNA repair processesPoly(ADP)-ribose polymerase inhibitorsCpG islandsTumor cell killingPreiss-HandlerCell line modelsAntitumor efficacy of a sequence-specific DNA-targeted γPNA-based c-Myc inhibitor
Malik S, Pradeep S, Kumar V, Xiao Y, Deng Y, Fan R, Vasquez J, Singh V, Bahal R. Antitumor efficacy of a sequence-specific DNA-targeted γPNA-based c-Myc inhibitor. Cell Reports Medicine 2024, 5: 101354. PMID: 38183981, PMCID: PMC10829792, DOI: 10.1016/j.xcrm.2023.101354.Peer-Reviewed Original ResearchConceptsTarget genomic DNAGenomic DNASequencing of genomic DNAGenomic DNA levelInhibit c-myc transcriptionC-myc transcriptionGenomic DNA targetsTarget oncogenesMultiple cell linesC-Myc inhibitorCancer therapyHistone deacetylase inhibitorsRNA targetsDNA targetsPatient-derived xenograftsPre-clinical modelsDNADeacetylase inhibitorsCell linesOncogeneInhibiting oncogenesDNA levelsAntitumor efficacyPrecision medicineChemotherapeutic drugs
2023
MODL-02. DEVELOPMENT OF RODENT GLIOBLASTOMA MODELS OF MGMT-MEDIATED TEMOZOLOMIDE RESISTANCE
Lee T, Bhatt D, Sundaram R, Saltzman W, Bindra R, Vasquez J. MODL-02. DEVELOPMENT OF RODENT GLIOBLASTOMA MODELS OF MGMT-MEDIATED TEMOZOLOMIDE RESISTANCE. Neuro-Oncology 2023, 25: v298-v298. PMCID: PMC10640218, DOI: 10.1093/neuonc/noad179.1153.Peer-Reviewed Original ResearchMouse glioma modelPotential therapeutic targetMGMT overexpressionGlioma modelTherapeutic targetTumor growthDaily x 5 daysMGMT expressionMGMT inhibitorsUseful preclinical toolTumor immune microenvironmentImportant prognostic biomarkerFischer 344 ratsHuman GBM cell linesDelays tumor growthHigh MGMT expressionMouse glioma cellsRodent glioblastoma modelsSyngeneic Fischer 344 ratsGBM cell linesAlkylator therapyO6-methylguanine-DNA methyltransferaseChemoimmunotherapy combinationImmune microenvironmentSyngeneic modelUse of stereotactic radiosurgery in treatment of brain metastases from pediatric extracranial solid tumors
Xu S, Campbell A, Chiang V, Bindra R, Vasquez J, Pashankar F. Use of stereotactic radiosurgery in treatment of brain metastases from pediatric extracranial solid tumors. Pediatric Blood & Cancer 2023, 70: e30303. PMID: 36975152, DOI: 10.1002/pbc.30303.Peer-Reviewed Original ResearchRhabdomyosarcoma with isolated lung metastases: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group
Vasquez J, Luo L, Hiniker S, Rhee D, Dasgupta R, Chen S, Weigel B, Xue W, Venkatramani R, Arndt C. Rhabdomyosarcoma with isolated lung metastases: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. Pediatric Blood & Cancer 2023, 70: e30293. PMID: 36916768, PMCID: PMC10424503, DOI: 10.1002/pbc.30293.Peer-Reviewed Original ResearchConceptsEvent-free survivalMetastatic diseaseYears of ageOverall survivalOncology GroupLung metastasesExact testSoft Tissue Sarcoma CommitteeSuperior event-free survivalBetter survival outcomesKaplan-Meier methodChildren's Oncology GroupRisk stratification algorithmLog-rank testOutcome of childrenFisher's exact testN0 diseaseAggressive treatmentMetastatic rhabdomyosarcomaExtrapulmonary sitesMetastatic sitesExtremity tumorsSurvival outcomesEmbryonal histologyCOG protocols
2022
The Role of PARP Inhibitors in Patients with Primary Malignant Central Nervous System Tumors
Gueble SE, Vasquez JC, Bindra RS. The Role of PARP Inhibitors in Patients with Primary Malignant Central Nervous System Tumors. Current Treatment Options In Oncology 2022, 23: 1566-1589. PMID: 36242713, DOI: 10.1007/s11864-022-01024-5.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHomologous recombination deficiencyPrimary CNS tumorsCNS tumorsClinical trialsPARP inhibitorsPreclinical evidencePrimary malignant central nervous system tumorMalignant central nervous system tumorsCentral nervous system tumorsImmune checkpoint inhibitorsStandard treatment modalityInitial clinical trialsEarly phase trialsNervous system tumorsCentral nervous tumorsExtracranial cancerCheckpoint inhibitorsDevastating malignancyStandard therapyOngoing trialsCombination therapyTreatment optionsTreatment modalitiesSystem tumorsPhase trialsMetastatic and multiply relapsed SDH‐deficient GIST and paraganglioma displays clinical response to combined poly ADP‐ribose polymerase inhibition and temozolomide
Singh C, Bindra RS, Glazer PM, Vasquez JC, Pashankar F. Metastatic and multiply relapsed SDH‐deficient GIST and paraganglioma displays clinical response to combined poly ADP‐ribose polymerase inhibition and temozolomide. Pediatric Blood & Cancer 2022, 70: e30020. PMID: 36151992, DOI: 10.1002/pbc.30020.Peer-Reviewed Original ResearchTargeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy
Ueno D, Vasquez JC, Sule A, Liang J, van Doorn J, Sundaram R, Friedman S, Caliliw R, Ohtake S, Bao X, Li J, Ye H, Boyd K, Huang RR, Dodson J, Boutros P, Bindra RS, Shuch B. Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy. Oncotarget 2022, 13: 1054-1067. PMID: 36128328, PMCID: PMC9477221, DOI: 10.18632/oncotarget.28273.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Diphosphate RiboseAnimalsCarcinoma, Renal CellCitric Acid CycleDioxygenasesDNAFumarate HydrataseFumaratesHumansJumonji Domain-Containing Histone DemethylasesKidney NeoplasmsLysineMicePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsSuccinate DehydrogenaseSuccinatesTemozolomideConceptsRenal cell carcinomaPoly ADP-ribose polymerase inhibitorsADP-ribose polymerase inhibitorsCell carcinomaSDH-deficient renal cell carcinomaPolymerase inhibitorsLow-dose temozolomideAggressive renal cell carcinomaHereditary cancer syndromesNovel therapeutic strategiesDeficient murine modelStandard dosingTMZ resultsMurine modelTherapeutic strategiesCombination treatmentCancer syndromesTumor growthHomologous recombination DNA repair pathwayAccumulation of fumarateHR deficiencyPARP inhibitionTemozolomideChemotherapyCarcinomaTOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor.
Jo U, Murai Y, Agama KK, Sun Y, Saha LK, Yang X, Arakawa Y, Gayle S, Jones K, Paralkar V, Sundaram RK, Van Doorn J, Vasquez JC, Bindra RS, Choi WS, Pommier Y. TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor. Molecular Cancer Therapeutics 2022, 21: 1090-1102. PMID: 35439320, PMCID: PMC9256811, DOI: 10.1158/1535-7163.mct-21-1000.Peer-Reviewed Original ResearchConceptsATR inhibitorsTop1 inhibitorsHomologous recombination deficiencyNovel molecular interactionApoptotic cell deathCancer cellsTop1 cleavage complexesAtaxia telangiectasiaCleavage complexesCell deathDNA damageHigher DNA damageMolecular interactionsDNA baseKinase inhibitorsI inhibitorMolecular pharmacologyMouse xenograftsTOP1Recombination deficiencyTopoisomerase I inhibitorInhibitorsTumor growthRad3Predictive biomarkers
2021
Targeting IDH1/2 mutant cancers with combinations of ATR and PARP inhibitors
Sule A, Van Doorn J, Sundaram RK, Ganesa S, Vasquez JC, Bindra RS. Targeting IDH1/2 mutant cancers with combinations of ATR and PARP inhibitors. NAR Cancer 2021, 3: zcab018. PMID: 34027408, PMCID: PMC8127964, DOI: 10.1093/narcan/zcab018.Peer-Reviewed Original Research
2020
Risk associated alterations in marrow T cells in pediatric leukemia
Bailur JK, McCachren SS, Pendleton K, Vasquez JC, Lim H, Duffy A, Doxie D, Kaushal A, Foster C, DeRyckere D, Castellino S, Kemp ML, Qiu P, Dhodapkar M, Dhodapkar K. Risk associated alterations in marrow T cells in pediatric leukemia. JCI Insight 2020, 5: e140179. PMID: 32692727, PMCID: PMC7455136, DOI: 10.1172/jci.insight.140179.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentBone MarrowCase-Control StudiesChildChild, PreschoolFemaleGene Expression ProfilingHumansInfantKiller Cells, NaturalLeukemia, Myeloid, AcuteMalePrecursor Cell Lymphoblastic Leukemia-LymphomaReproducibility of ResultsRisk FactorsSingle-Cell AnalysisT-LymphocytesTumor MicroenvironmentConceptsAcute lymphoblastic leukemiaNaive T cellsT cellsDisease riskChildhood leukemiaLymphoblastic leukemiaStem-like memory T cellsTerminal effector T cellsB-cell acute lymphoblastic leukemiaChronic immune activationCell acute lymphoblastic leukemiaEffector T cellsMarrow T cellsMemory T cellsAcute myelogenous leukemiaEvidence of dysfunctionStem-like genesImmune signaturesNK cellsClinical featuresImmune environmentImmune landscapeImmune therapyImmune activationImmune microenvironmentSubtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma
Robinson MH, Vasquez J, Kaushal A, MacDonald TJ, Vega J, Schniederjan M, Dhodapkar K. Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma. Journal For ImmunoTherapy Of Cancer 2020, 8: e001066. PMID: 32788236, PMCID: PMC7422651, DOI: 10.1136/jitc-2020-001066.Peer-Reviewed Original ResearchConceptsT cell infiltrationHigh-grade gliomasT-cell densityLow-grade tumorsT cellsGlial tumorsTissue-resident memory T cellsTumor-resident T cellsPediatric gliomasTumor-infiltrating T cellsMemory T cellsCancer-related mortalityPediatric glial tumorsSingle-cell mass cytometryExpression of SOX2Stem cell markersImmune controlImmune therapyRecurrent tumorsImmune cellsImmunofluorescence immunohistochemistryPleomorphic xanthoastrocytomaBrain tumorsImmune architectureAdult gliomasPersistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma
Hong CS, Vasquez JC, Kundishora AJ, Elsamadicy AA, Beckta JM, Sule A, Marks AM, Leelatian N, Huttner A, Bindra RS, DiLuna ML, Kahle KT, Erson-Omay EZ. Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma. Npj Genomic Medicine 2020, 5: 23. PMID: 32528726, PMCID: PMC7264170, DOI: 10.1038/s41525-020-0130-7.Peer-Reviewed Original ResearchPediatric patientsStandard chemoradiationSTAG2 mutationsTumor clonesPediatric glioblastomaGross total resectionMultiple surgical resectionsTime of recurrenceHigh-grade gliomasDNA damage repair defectsWhole-exome sequencingVariety of treatmentsSurgical resectionNovel deleterious mutationsStandard therapyTotal resectionVaccine therapyClinical evidencePreclinical dataTreatment optionsMultimodal therapyPreclinical studiesClinical settingTherapyAdult counterparts
2017
Sinusoidal Obstruction Syndrome During Maintenance Therapy for Acute Lymphoblastic Leukemia With 6-Mercaptopurine and Methotrexate: A Pediatric Case Report.
McNerney KO, Vasquez JC, Kent MW, McNamara JM. Sinusoidal Obstruction Syndrome During Maintenance Therapy for Acute Lymphoblastic Leukemia With 6-Mercaptopurine and Methotrexate: A Pediatric Case Report. Journal Of Pediatric Hematology/oncology 2017, 39: e454-e455. PMID: 28085749, DOI: 10.1097/MPH.0000000000000776.Peer-Reviewed Original ResearchSOX2 immunity and tissue resident memory in children and young adults with glioma
Vasquez JC, Huttner A, Zhang L, Marks A, Chan A, Baehring JM, Kahle KT, Dhodapkar KM. SOX2 immunity and tissue resident memory in children and young adults with glioma. Journal Of Neuro-Oncology 2017, 134: 41-53. PMID: 28620836, PMCID: PMC7906294, DOI: 10.1007/s11060-017-2515-8.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAntigen-Presenting CellsB7-H1 AntigenBrain NeoplasmsCell ProliferationChildChild, PreschoolCytokinesFemaleFlow CytometryGliomaHumansInfantMaleMyeloid CellsProgrammed Cell Death 1 ReceptorReceptors, ImmunologicRNA, Small InterferingSOXB1 Transcription FactorsT-LymphocytesTransfectionYoung AdultConceptsPediatric glial tumorsGlial tumorsT cellsExpression of SOX2Inhibitory checkpointsCD8/CD4 T cellsTissue-resident memory phenotypeTumor-infiltrating immune cellsTumor-infiltrating T cellsTumor cellsYoung adultsResident memory phenotypeTissue-resident memoryAnti-tumor immunityT cell immunityCD4 T cellsNatural killer cellsGlial tumor cellsNew antigenic targetsSingle-cell mass cytometryHigh mutation burdenStem cell antigenGlioma initiating cellsImmune checkpointsPD-1SOX2 as a target for immunotherapy of pediatric gliomas.
Vasquez J, Huttner A, Zhang L, Marks A, Chan A, Baehring J, Kahle K, Dhodapkar K. SOX2 as a target for immunotherapy of pediatric gliomas. Journal Of Clinical Oncology 2017, 35: e22012-e22012. DOI: 10.1200/jco.2017.35.15_suppl.e22012.Peer-Reviewed Original ResearchTumor-infiltrating T cellsImmune checkpoint blockadeT cellsPediatric glial tumorsGlial tumorsExpression of SOX2Inhibitory checkpointsCheckpoint blockadeTumor immunityGrade gliomasTissue-resident memory phenotypePediatric gliomasTumor-infiltrating immune cellsTumor cellsResident memory phenotypeT-cell proliferation assaysImmune checkpoint inhibitorsDendritic cell vaccinesPD-1 expressionSubset of CD4Anti-tumor immunityCD8 T cellsT cell immunityEffective tumor immunityPediatric brain tumors
2016
ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells
Boddupalli CS, Nair S, Gray SM, Nowyhed HN, Verma R, Gibson JA, Abraham C, Narayan D, Vasquez J, Hedrick CC, Flavell RA, Dhodapkar KM, Kaech SM, Dhodapkar MV. ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells. Journal Of Clinical Investigation 2016, 126: 3905-3916. PMID: 27617863, PMCID: PMC5096804, DOI: 10.1172/jci85329.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsMemory T cellsT cellsTRM cellsCellular therapyAdoptive cellular therapyImmune-deficient micePotential cellular therapySP T cellsSide population cellsHuman T cellsPutative subsetsAdoptive transferDistinct gene expression profilesCell mobilizationImmune surveillanceQuiescent subsetPopulation cellsMiceTherapyQuiescent phenotypeDistinct subsetsMember 1Nuclear receptorsSignature genes
2015
Clinical and pharmacodynamic analysis of pomalidomide dosing strategies in myeloma: impact of immune activation and cereblon targets
Sehgal K, Das R, Zhang L, Verma R, Deng Y, Kocoglu M, Vasquez J, Koduru S, Ren Y, Wang M, Couto S, Breider M, Hansel D, Seropian S, Cooper D, Thakurta A, Yao X, Dhodapkar KM, Dhodapkar MV. Clinical and pharmacodynamic analysis of pomalidomide dosing strategies in myeloma: impact of immune activation and cereblon targets. Blood 2015, 125: 4042-4051. PMID: 25869284, PMCID: PMC4481593, DOI: 10.1182/blood-2014-11-611426.Peer-Reviewed Original ResearchConceptsImmune activationAntitumor effectsNK cellsT cellsMore frequent adverse eventsClinical antitumor effectsFrequent adverse eventsNatural killer cellsIntermittent dosing strategyDirect antitumor effectsExpression of cytokinesT cell activationGreater tumor reductionPomalidomide/Coinhibitory receptorsAdverse eventsClinical responseOverall survivalKiller cellsPharmacodynamic effectsImmunomodulatory effectsMultiple myelomaTumor reductionIntermittent dosingPharmacodynamic analysis