2025
More than just another IDH inhibitor: Insights from the HMPL-306 phase 1 trial
Getz T, Bewersdorf J. More than just another IDH inhibitor: Insights from the HMPL-306 phase 1 trial. Med 2025, 6: 100600. PMID: 40516517, DOI: 10.1016/j.medj.2025.100600.Peer-Reviewed Original Research
2024
Epigenetics-targeted drugs: current paradigms and future challenges
Dai W, Qiao X, Fang Y, Guo R, Bai P, Liu S, Li T, Jiang Y, Wei S, Na Z, Xiao X, Li D. Epigenetics-targeted drugs: current paradigms and future challenges. Signal Transduction And Targeted Therapy 2024, 9: 332. PMID: 39592582, PMCID: PMC11627502, DOI: 10.1038/s41392-024-02039-0.Peer-Reviewed Original ResearchConceptsNon-coding RNA regulationDNA base sequenceRNA modificationsRNA regulationChromatin remodelingHistone modificationsEnhancer of zeste homolog 2Epigenetic landscapeGenetic informationOrganismal developmentDNA methyltransferasesEpigenetic enzymesDNA modificationsBase sequenceHomolog 2Zeste homolog 2Histone deacetylasesHuman diseasesIsocitrate dehydrogenaseDNAPathological contextsRegulatory systemChromatinEnzymeHistone
2022
A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation
Yanchus C, Drucker K, Kollmeyer T, Tsai R, Winick-Ng W, Liang M, Malik A, Pawling J, De Lorenzo S, Ali A, Decker P, Kosel M, Panda A, Al-Zahrani K, Jiang L, Browning J, Lowden C, Geuenich M, Hernandez J, Gosio J, Ahmed M, Loganathan S, Berman J, Trcka D, Michealraj K, Fortin J, Carson B, Hollingsworth E, Jacinto S, Mazrooei P, Zhou L, Elia A, Lupien M, He H, Murphy D, Wang L, Abyzov A, Dennis J, Maass P, Campbell K, Wilson M, Lachance D, Wrensch M, Wiencke J, Mak T, Pennacchio L, Dickel D, Visel A, Wrana J, Taylor M, Zadeh G, Dirks P, Eckel-Passow J, Attisano L, Pombo A, Ida C, Kvon E, Jenkins R, Schramek D. A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation. Science 2022, 378: 68-78. PMID: 36201590, PMCID: PMC9926876, DOI: 10.1126/science.abj2890.Peer-Reviewed Original ResearchConceptsNoncoding single nucleotide polymorphismSingle nucleotide polymorphismsCausal variantsMolecular pathwaysIsocitrate dehydrogenaseLethal gliomaHeritable predispositionGlioma formationTumor developmentLow-grade gliomasMutant lower grade gliomasPolymorphismMouse modelPromoterLociEnhancerSixfold greater riskRs55705857PathwayMechanisticallyDehydrogenaseDisruptsExpressionPenetranceCancer riskGlioma progression is shaped by genetic evolution and microenvironment interactions
Varn F, Johnson K, Martinek J, Huse J, Nasrallah M, Wesseling P, Cooper L, Malta T, Wade T, Sabedot T, Brat D, Gould P, Wöehrer A, Aldape K, Ismail A, Sivajothi S, Barthel F, Kim H, Kocakavuk E, Ahmed N, White K, Datta I, Moon H, Pollock S, Goldfarb C, Lee G, Garofano L, Anderson K, Nehar-Belaid D, Barnholtz-Sloan J, Bakas S, Byrne A, D’Angelo F, Gan H, Khasraw M, Migliozzi S, Ormond D, Paek S, Van Meir E, Walenkamp A, Watts C, Weiss T, Weller M, Palucka K, Stead L, Poisson L, Noushmehr H, Iavarone A, Verhaak R, Consortium T, Varn F, Johnson K, Martinek J, Huse J, Nasrallah M, Wesseling P, Cooper L, Malta T, Wade T, Sabedot T, Brat D, Gould P, Wöehrer A, Aldape K, Ismail A, Sivajothi S, Barthel F, Kim H, Kocakavuk E, Ahmed N, White K, Datta I, Moon H, Pollock S, Goldfarb C, Lee G, Garofano L, Anderson K, Nehar-Belaid D, Barnholtz-Sloan J, Bakas S, Byrne A, D’Angelo F, Gan H, Khasraw M, Migliozzi S, Ormond D, Paek S, Van Meir E, Walenkamp A, Watts C, Weiss T, Weller M, Alfaro K, Amin S, Ashley D, Bock C, Brodbelt A, Bulsara K, Castro A, Connelly J, Costello J, de Groot J, Finocchiaro G, French P, Golebiewska A, Hau A, Hong C, Horbinski C, Kannan K, Kouwenhoven M, Lasorella A, LaViolette P, Ligon K, Lowman A, Mehta S, Miletic H, Molinaro A, Ng H, Niclou S, Niers J, Phillips J, Rabadan R, Rao G, Reifenberger G, Sanai N, Short S, Smitt P, Sloan A, Smits M, Snyder J, Suzuki H, Tabatabai G, Tanner G, Tomaszewski W, Wells M, Westerman B, Wheeler H, Xie J, Yung W, Zadeh G, Zhao J, Palucka K, Stead L, Poisson L, Noushmehr H, Iavarone A, Verhaak R. Glioma progression is shaped by genetic evolution and microenvironment interactions. Cell 2022, 185: 2184-2199.e16. PMID: 35649412, PMCID: PMC9189056, DOI: 10.1016/j.cell.2022.04.038.Peer-Reviewed Original ResearchConceptsSpecific ligand-receptor interactionsMicroenvironment interactionsDNA sequencing dataGlioma progressionLigand-receptor interactionsNeoplastic cellsSignaling programsCell statesSequencing dataGenetic evolutionGenetic changesIDH wild-type tumorsIsocitrate dehydrogenaseMesenchymal transitionSomatic alterationsDistinct mannerActive tumor growthIDH-mutant gliomasPotential targetTherapy resistanceAdult patientsDisease progressionPossible roleCellsTumor growth
2020
Targeting therapeutic vulnerabilities with PARP inhibition and radiation in IDH-mutant gliomas and cholangiocarcinomas
Wang Y, Wild A, Turcan S, Wu W, Sigel C, Klimstra D, Ma X, Gong Y, Holland E, Huse J, Chan T. Targeting therapeutic vulnerabilities with PARP inhibition and radiation in IDH-mutant gliomas and cholangiocarcinomas. Science Advances 2020, 6: eaaz3221. PMID: 32494639, PMCID: PMC7176409, DOI: 10.1126/sciadv.aaz3221.Peer-Reviewed Original ResearchIDH-mutant gliomasIsocitrate dehydrogenaseAnimal models of gliomaReduced DNA damage repairRibose polymerase inhibitorsLocal radiation therapyTarget solid tumorsPreclinical animal modelsIsocitrate dehydrogenase mutationModel of gliomaMutant isocitrate dehydrogenaseSynthetic lethal approachTargetable therapeutic vulnerabilitiesDNA damage repairMultiple cancer typesRadiation therapyMultimodal therapyMultiple in vitroSolid tumorsElevated DNA damageTherapeutic vulnerabilitiesTumor cellsPARP inhibitionTreatment strategiesPolymerase inhibitorsIn vivo MRS measurement of 2‐hydroxyglutarate in patient‐derived IDH‐mutant xenograft mouse models versus glioma patients
Tiwari V, Mashimo T, An Z, Vemireddy V, Piccirillo S, Askari P, Hulsey K, Zhang S, de Graaf R, Patel T, Pan E, Mickey B, Maher E, Bachoo R, Choi C. In vivo MRS measurement of 2‐hydroxyglutarate in patient‐derived IDH‐mutant xenograft mouse models versus glioma patients. Magnetic Resonance In Medicine 2020, 84: 1152-1160. PMID: 32003035, PMCID: PMC7263951, DOI: 10.1002/mrm.28183.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsPatient-derived xenograft micePreclinical modelsGlioma patientsPatient-derived xenograft tumorsPatient-derived xenograft modelsDetection of 2HGIDH1 R132H mutationShort-TE MRSXenograft mouse modelMutant gliomasR132H mutationIDH-mutantIn vivo MRS measurementsMouse modelPhantom analysisMetabolic reprogrammingPatientsMetabolite levelsGliomaMiceMetabolic fingerprintsPRESS sequenceIsocitrate dehydrogenaseMRS methodsExpression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes
Frenster J, Kader M, Kamen S, Sun J, Chiriboga L, Serrano J, Bready D, Golub D, Ravn-Boess N, Stephan G, S A, Kurz S, Jain R, Park C, Fenyo D, Liebscher I, Schöneberg T, Wiggin G, Newman R, Barnes M, Dickson J, MacNeil D, Huang X, Shohdy N, Snuderl M, Zagzag D, Placantonakis D. Expression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes. Neuro-Oncology Advances 2020, 2: vdaa053. PMID: 32642706, PMCID: PMC7262742, DOI: 10.1093/noajnl/vdaa053.Peer-Reviewed Original ResearchAdult gliomasIsocitrate dehydrogenase wild-type tumorsWild-type tumorsLimited treatment optionsBrain tissueNon-neoplastic brain tissuesTumor bulkAdvanced malignanciesGlioma familiesTumor specimensTumor marginsMutant gliomasAdult glioblastomaWHO gradeNovel therapiesTreatment optionsTumor growthGlioma subtypesBrain malignanciesTumorGliomaWild-typeIsocitrate dehydrogenaseMalignancyGlioblastoma
1993
Incomplete citric acid cycle obliges aminolevulinic acid synthesis via the C5 pathway in a methylotroph
Lloyd A, Weitzman P, Söll D. Incomplete citric acid cycle obliges aminolevulinic acid synthesis via the C5 pathway in a methylotroph. Microbiology 1993, 139: 2931-2938. DOI: 10.1099/00221287-139-12-2931.Peer-Reviewed Original ResearchC5 pathwayM. methylotrophusAminolevulinic acid synthesisTRNA-dependent mannerConversion of pyruvateCitric acid cycleMalate dehydrogenase activityMammalian cellsGlyoxylate cycleALA formationCell-free extractsGlu-tRNAGluAcid cycleIsocitrate dehydrogenaseMethylophilus methylotrophusCatabolic roleAcid synthesisPathwayEnzymic activityDehydrogenase activityEnzymeConnected pathwaysAlaMethylotrophsYeast
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