2024
EXTH-23. NEW DNA-CROSSLINKING CHEMOTHERAPY IS EFFECTIVE AGAINST POST-TEMOZOLOMIDE MISMATCH REPAIR-DEFICIENT PATIENT-DERIVED HYPERMUTANT GLIOMAS
McCord M, Wang W, An S, Sears T, Sarkaria J, James C, Ruggieri B, Bindra R, Horbinski C. EXTH-23. NEW DNA-CROSSLINKING CHEMOTHERAPY IS EFFECTIVE AGAINST POST-TEMOZOLOMIDE MISMATCH REPAIR-DEFICIENT PATIENT-DERIVED HYPERMUTANT GLIOMAS. Neuro-Oncology 2024, 26: viii241-viii241. PMCID: PMC11553709, DOI: 10.1093/neuonc/noae165.0954.Peer-Reviewed Original ResearchPatient-derived xenograftsDNA inter-strand cross-linksMismatch repairDNA mismatch repairGlioblastoma cell linesBase mismatchesShRNA knockdownGlioblastoma patient-derived xenograftsMGMT deficiencyMGMT-deficient cellsDNA damageInter-strand cross-linksDNAMMR-deficient tumor cellsCell linesPatient-derived xenograft modelsComplementary in vitro studiesAlkylating agent temozolomideMMR genesVehicle control miceDays post-engraftmentApoptosisMismatch repair mutationsDNA basesResistance to temozolomidePARG inhibition induces nuclear aggregation of PARylated PARP1
Paradkar S, Purcell J, Cui A, Friedman S, Noronha K, Murray M, Sundaram R, Bindra R, Jensen R. PARG inhibition induces nuclear aggregation of PARylated PARP1. Structure 2024, 32: 2083-2093.e5. PMID: 39406247, DOI: 10.1016/j.str.2024.09.006.Peer-Reviewed Original ResearchDNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology
Rahman R, Shi D, Reitman Z, Hamerlik P, de Groot J, Haas-Kogan D, D’Andrea A, Sulman E, Tanner K, Agar N, Sarkaria J, Tinkle C, Bindra R, Mehta M, Wen P. DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology. Neuro-Oncology 2024, 26: 1367-1387. PMID: 38770568, PMCID: PMC11300028, DOI: 10.1093/neuonc/noae072.Peer-Reviewed Original ResearchConsensus reviewDNA damage responseIDH wild-type glioblastomaIDH-mutant gliomasClinical trial design considerationsMechanisms of resistanceTrial design considerationsCombination therapyDevelopment of DDR inhibitorsDNA damage response pathwayPreclinical modelsDamage responseDDR inhibitorsNeuro-oncologyBrain tumorsBiomarker developmentTherapyResponse to DNA damageDNA damageTranslational effortsTumor
2015
Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors
Goglia AG, Delsite R, Luz AN, Shahbazian D, Salem AF, Sundaram RK, Chiaravalli J, Hendrikx PJ, Wilshire JA, Jasin M, Kluger HM, Glickman JF, Powell SN, Bindra RS. Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors. Molecular Cancer Therapeutics 2015, 14: 326-342. PMID: 25512618, PMCID: PMC4326563, DOI: 10.1158/1535-7163.mct-14-0765.Peer-Reviewed Original ResearchConceptsDSB repair inhibitorsDouble-strand breaksDSB repairHomologous recombinationRepair inhibitorsCell-based small molecule screenSuccessful DSB repairDNA-damaging agentsPlate-based formatCell-based screenSmall-molecule screenGenomic integrityTumor cell survivalMammalian cellsHR repairDNA repairMolecule screenReporter systemSecondary assaysCell survivalDNA damageCancer cell linesTumor cellsNovel hitsMost cancer therapies
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
2009
Targeting the DNA damage response for cancer therapy
Powell SN, Bindra RS. Targeting the DNA damage response for cancer therapy. DNA Repair 2009, 8: 1153-1165. PMID: 19501553, DOI: 10.1016/j.dnarep.2009.04.011.Peer-Reviewed Original ResearchConceptsDNA damage responseCell cycle checkpointsDouble-strand breaksGenome integrityGenomic integrityHistone modificationsDamage responseCycle checkpointsDNA repairKey proteinsDNA damageAnti-cancer agentsHuman tumorsNew anti-cancer agentsPathwayCancer therapyTumor cellsCheckpointProteinTherapeutic interventionsRepairIntegrityDefectsCellsAppropriate response
2005
Hypoxia-Induced Phosphorylation of Chk2 in an Ataxia Telangiectasia Mutated–Dependent Manner
Gibson SL, Bindra RS, Glazer PM. Hypoxia-Induced Phosphorylation of Chk2 in an Ataxia Telangiectasia Mutated–Dependent Manner. Cancer Research 2005, 65: 10734-10741. PMID: 16322218, DOI: 10.1158/0008-5472.can-05-1160.Peer-Reviewed Original ResearchConceptsDNA repairAtaxia telangiectasiaSerine/threonine kinaseDNA damageRelated kinase ATMKinase ataxia telangiectasiaNBS1-dependent mannerDNA repair factorsPhosphorylation of Chk2Hypoxic growth conditionsKinase ATMThreonine kinaseChk2 activationReplication forksRepair factorsChk2Apoptotic pathwayCell survivalNovel pathwayCycle arrestPhosphorylationGrowth conditionsDependent mannerPathwayCellsGenetic instability and the tumor microenvironment: towards the concept of microenvironment-induced mutagenesis
Bindra RS, Glazer PM. Genetic instability and the tumor microenvironment: towards the concept of microenvironment-induced mutagenesis. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 2005, 569: 75-85. PMID: 15603753, DOI: 10.1016/j.mrfmmm.2004.03.013.Peer-Reviewed Original ResearchConceptsGenetic instabilitySuch genetic instabilityDNA repair pathwaysOxidative base damageSuch DNA lesionsGenome integrityTumor microenvironmentRepair pathwaysDNA strand breaksDNA lesionsBase damageDNA damageStrand breaksMutagenesisInduction of mutagenesisAdverse conditionsTumor progressionMicroenvironmentRecent studiesSignificant threatPotential mechanismsNumerous typesInductionPathway