2017
2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity
Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 2017, 9 PMID: 28148839, PMCID: PMC5435119, DOI: 10.1126/scitranslmed.aal2463.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1PARP inhibitor sensitivityPossible therapeutic strategiesHomologous recombination defectsTherapeutic strategiesTumor xenograftsInhibitor sensitivityPathologic processesSmall molecule inhibitorsIDH1/2 mutationsTumor progressionIDH2 mutationsMutant IDHPolymerase inhibitorsGlioma cellsTumor cellsHR deficiencyPARP inhibitionIDH mutationsInhibitory effectDehydrogenase 1Neomorphic activityMutant IDH1 enzymeDependent dioxygenasesMutant cells
2010
Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130
Hegan DC, Lu Y, Stachelek GC, Crosby ME, Bindra RS, Glazer PM. Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 2201-2206. PMID: 20133863, PMCID: PMC2836641, DOI: 10.1073/pnas.0904783107.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorColonic NeoplasmsCrk-Associated Substrate ProteinDNA RepairDown-RegulationE2F4 Transcription FactorEnzyme InhibitorsGenes, BRCA1HumansPhenanthrenesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesPromoter Regions, GeneticRad51 RecombinaseRadiation-Sensitizing AgentsRNA, Small InterferingConceptsHomology-dependent repairBase excision repair factorsExcision repair factorsPARP inhibitionRole of PARPPARP inhibitorsRepair factorsExpression of BRCA1DNA repairDNA breaksHypoxic cancer cellsRAD51SiRNA knockdownDNA damagePARP-1P130 expressionCancer therapyP130Cancer cellsPARPRad51 promoterHPV E7BRCA1E7 expressionSiRNAs