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 model
2022
Antigen-independent tumor targeting by CBX-12 (alphalex™–exatecan) induces long-term antitumor immunity
Gayle S, Paradis T, Jones K, Vasquez J, Paralkar V. Antigen-independent tumor targeting by CBX-12 (alphalex™–exatecan) induces long-term antitumor immunity. Immunotherapy 2022, 14: 1467-1480. PMID: 36597724, DOI: 10.2217/imt-2022-0121.Peer-Reviewed Original ResearchConceptsLong-term antitumor immunityAntitumor immunityImmune recognition of tumor cellsInducer of immunogenic cell deathRecognition of tumor cellsAnti-PD-1Immunogenic cell deathDelayed tumor growthExpression of MHC-1Immunotherapy combinationsPH-sensitive peptidesComplete responseCT26 modelPD-L1Tumor cellsTumor targetingTumor growthCured animalsClinical trialsELISA assayImmunotherapyMHC-1Cell deathFunctional assaysImmunityTargeting 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