2022
Chapter 11 Oncometabolites, epigenetic marks, and DNA repair
Dow J, Glazer P. Chapter 11 Oncometabolites, epigenetic marks, and DNA repair. 2022, 191-202. DOI: 10.1016/b978-0-323-91081-1.00008-x.Peer-Reviewed Original ResearchDNA damage repairJmjC domain-containing histone demethylasesDamage repairDouble-strand break sitesHallmarks of cancerEpigenetic marksHistone demethylasesEpigenetic signalingDNA demethylaseDependent dioxygenasesEpigenetic mechanismsDNA repairMajor translational impactGenomic instabilityMethylation signalsRepair pathwaysBreak siteDNA hypermethylationDNA damageΑ-ketoglutarateGlobal histoneOncometaboliteCancer cellsCompetitive inhibitorProfound sensitivity
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