2024
The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma
McCord M, Sears T, Wang W, Chaliparambil R, An S, Sarkaria J, James C, Ruggeri B, Gueble S, Bindra R, Horbinski C. The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma. Neuro-Oncology 2024, noae257. PMID: 39658092, DOI: 10.1093/neuonc/noae257.Peer-Reviewed Original ResearchMedian survival of miceSurvival of miceMedian survivalIDH wild-type glioblastomaO-6-methylguanine-DNA methyltransferaseExposure to temozolomideAcquired resistance to TMZWild-type glioblastomaPatient-derived xenograftsSensitivity to temozolomidePatient-derived modelsResistance to temozolomideLN229 glioma cellsPatient-derived glioblastomaRecurrent tumorsMGMT deficiencyFractionated RTTemozolomideLow dosesImprove outcomesGlioblastomaEnzyme deficiencyMismatch repairGlioma cellsGBM12EXTH-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 temozolomideO6-Guanine Targeting Novel DNA Cross-Linker and ATR Inhibitor Combination for MGMT-Silenced IDH1/2 Mutant Acute Myeloid Leukemia
Bhardwaj P, Sundaram R, Friedman S, Baassiri A, Matthews M, VanOudenhove J, Gueble S, Halene S, Bindra R. O6-Guanine Targeting Novel DNA Cross-Linker and ATR Inhibitor Combination for MGMT-Silenced IDH1/2 Mutant Acute Myeloid Leukemia. Blood 2024, 144: 6130. DOI: 10.1182/blood-2024-210621.Peer-Reviewed Original ResearchAML patient samplesHematologic adverse effectsMGMT promoter hypermethylationPatient-derived xenograftsDe novoMismatch repairO6 position of guaninePromoter hypermethylationMyelodysplastic syndromeRNA-seq analysisMyeloid leukemiaATR inhibitorsDNA repair proteinsClinical trialsSelection of mutationsFunctional mismatch repairPatient samplesMutant acute myeloid leukemiaBiomarker-targeted therapiesCell line pairsAlkylation DNA damageMutant IDH1/2 inhibitorsRNA-seqCases of AMLMGMT promoter methylation
2007
Regulation of DNA repair in hypoxic cancer cells
Bindra RS, Crosby ME, Glazer PM. Regulation of DNA repair in hypoxic cancer cells. Cancer And Metastasis Reviews 2007, 26: 249-260. PMID: 17415527, DOI: 10.1007/s10555-007-9061-3.Peer-Reviewed Original ResearchConceptsGenetic instabilityMismatch repairHypoxia-induced genetic instabilityDNA damage response factorsDamage response factorsDNA damage responseCellular stress responseATM/ATRDNA repair pathwaysHomologous recombination pathwayCancer cellsAcute DNA damage responseDNA mismatch repairTumor microenvironmental stressDamage responseKey genesHR repairDNA repairRepair pathwaysMicroenvironmental stressHypoxic cancer cellsStress responsePossible mechanistic explanationRecombination pathwayResponse factor