2020
Baseline requirements for novel agents being considered for phase II/III brain cancer efficacy trials: conclusions from the Adult Brain Tumor Consortium’s first workshop on CNS drug delivery
Grossman SA, Romo CG, Rudek MA, Supko J, Fisher J, Nabors LB, Wen PY, Peereboom DM, Ellingson BM, Elmquist W, Barker FG, Kamson D, Sarkaria JN, Timmer W, Bindra RS, Ye X. Baseline requirements for novel agents being considered for phase II/III brain cancer efficacy trials: conclusions from the Adult Brain Tumor Consortium’s first workshop on CNS drug delivery. Neuro-Oncology 2020, 22: 1422-1424. PMID: 32506123, PMCID: PMC7566550, DOI: 10.1093/neuonc/noaa142.Peer-Reviewed Original ResearchOncometabolites suppress DNA repair by disrupting local chromatin signalling
Sulkowski PL, Oeck S, Dow J, Economos NG, Mirfakhraie L, Liu Y, Noronha K, Bao X, Li J, Shuch BM, King MC, Bindra RS, Glazer PM. Oncometabolites suppress DNA repair by disrupting local chromatin signalling. Nature 2020, 582: 586-591. PMID: 32494005, PMCID: PMC7319896, DOI: 10.1038/s41586-020-2363-0.Peer-Reviewed Original ResearchConceptsDNA repairDNA breaksFumarate hydrataseDownstream repair factorsHistone 3 lysine 9Homology-dependent repairPoly (ADP-ribose) polymeraseRecruitment of TIP60Deregulation of metabolismChromatin signalingSuccinate dehydrogenase genesGenome integrityLysine 9Repair factorsDehydrogenase geneEnd resectionIsocitrate dehydrogenase 1Aberrant hypermethylationMechanistic basisSomatic mutationsDehydrogenase 1GenesHuman malignanciesProper executionMutationsEstimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer
Shuch B, Li S, Risch H, Bindra RS, McGillivray PD, Gerstein M. Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer. Cancer 2020, 126: 3657-3666. PMID: 32413184, PMCID: PMC10316675, DOI: 10.1002/cncr.32914.Peer-Reviewed Original ResearchConceptsFumarate hydrataseExome Aggregation ConsortiumAllele frequenciesFH geneGenome ProjectDifferent world populationsFH alterationsHereditary leiomyomatosisKidney cancer riskCancer penetranceMissense alterationsGenesOverall allele frequencyRare variantsLow penetranceRenal cancerExACKidney cancerCancer riskPenetranceGermline mutationsLethal formWorld populationCancer syndromesAlterationsGray Areas in the Gray Matter: IDH1/2 Mutations in Glioma.
van den Bent MJ, Mellinghoff IK, Bindra RS. Gray Areas in the Gray Matter: IDH1/2 Mutations in Glioma. American Society Of Clinical Oncology Educational Book 2020, 40: 1-8. PMID: 32186930, PMCID: PMC7673204, DOI: 10.1200/edbk_280967.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMutant IDH inhibitorsIDH inhibitorsMutant acute myeloid leukemiaPhase III trialsDistinct clinical characteristicsClinical characteristicsIII trialsCombination therapyPharmacologic blockadeClinical trialsMutant cancer cellsMyeloid leukemiaDiagnostic groupsGray matterCancer developmentMetabolic changesAntitumor activityCancer cellsGliomasHuman cancersClass inhibitorMutant gliomasTumorsIntracellular changesGlioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions
Wen PY, Weller M, Lee EQ, Alexander BM, Barnholtz-Sloan JS, Barthel FP, Batchelor TT, Bindra RS, Chang SM, Chiocca EA, Cloughesy TF, DeGroot JF, Galanis E, Gilbert MR, Hegi ME, Horbinski C, Huang RY, Lassman AB, Le Rhun E, Lim M, Mehta MP, Mellinghoff IK, Minniti G, Nathanson D, Platten M, Preusser M, Roth P, Sanson M, Schiff D, Short SC, Taphoorn MJB, Tonn JC, Tsang J, Verhaak RGW, von Deimling A, Wick W, Zadeh G, Reardon DA, Aldape KD, van den Bent MJ. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro-Oncology 2020, 22: 1073-1113. PMID: 32328653, PMCID: PMC7594557, DOI: 10.1093/neuonc/noaa106.Peer-Reviewed Original ResearchConceptsNeuro-oncologyConsensus reviewCurrent managementMalignant primary brain tumorIsocitrate dehydrogenase-wildtype glioblastomaPrimary brain tumorsNovel therapiesViral therapyBrain tumorsImportant causeMolecular pathogenesisMolecular therapyEuropean AssociationTherapyEuropean SocietyCommon formGlioblastomaWildtype glioblastomaTumorsFuture directionsImportant advancesImmunotherapyMorbidityPatientsDNA damage response
2019
Targeting DNA repair in gliomas.
Beckta JM, Bindra RS, Chalmers AJ. Targeting DNA repair in gliomas. Current Opinion In Neurology 2019, 32: 878-885. PMID: 31592790, DOI: 10.1097/wco.0000000000000760.Peer-Reviewed Original ResearchConceptsLocal controlPoor local controlBlood-brain barrierTreatment of gliomaOverall survivalSystemic treatmentClinical outcomesDismal prognosisAggressive entityPreclinical dataPatient outcomesRadiation therapyGliomasOutcomesDNA repair targetsTreatmentRepair mechanismsRepair targetsNovel chemoCurrent understandingPatientsPrognosisDNA damage responseMalignancyTemozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors
Jackson CB, Noorbakhsh SI, Sundaram RK, Kalathil AN, Ganesa S, Jia L, Breslin H, Burgenske DM, Gilad O, Sarkaria JN, Bindra RS. Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors. Cancer Research 2019, 79: 4331-4338. PMID: 31273061, PMCID: PMC6810597, DOI: 10.1158/0008-5472.can-18-3394.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, AlkylatingAntineoplastic Combined Chemotherapy ProtocolsAtaxia Telangiectasia Mutated ProteinsCell Cycle CheckpointsCell Line, TumorCheckpoint Kinase 1DNA Breaks, Double-StrandedDNA DamageDNA Modification MethylasesDNA Repair EnzymesDrug SynergismFemaleHumansIsoxazolesMice, NudePyrazinesTemozolomideTumor Suppressor ProteinsXenograft Model Antitumor AssaysConceptsMGMT-deficient cellsPPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma
Fons NR, Sundaram RK, Breuer GA, Peng S, McLean RL, Kalathil AN, Schmidt MS, Carvalho DM, Mackay A, Jones C, Carcaboso ÁM, Nazarian J, Berens ME, Brenner C, Bindra RS. PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma. Nature Communications 2019, 10: 3790. PMID: 31439867, PMCID: PMC6706443, DOI: 10.1038/s41467-019-11732-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBrain Stem NeoplasmsCell Line, TumorChildCytokinesDiffuse Intrinsic Pontine GliomaDNA MethylationEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticHumansMiceNicotinamide PhosphoribosyltransferasePonsPrimary Cell CultureProtein Phosphatase 2CSynthetic Lethal MutationsXenograft Model Antitumor AssaysConceptsNicotinic acid phosphoribosyltransferaseSynthetic lethal interactionsNAMPT inhibitorsTumor-specific cell killingProtein phosphataseEpigenetic silencingMutant cellsKey genesCpG islandsLethal interactionsNAD biosynthesisGene expressionInhibitor sensitivityNAD metabolismOncogenic rolePediatric gliomasMutationsModel systemCell killingDriver mutationsPediatric high-grade gliomasMutant tumorsOncogenic driver mutationsNicotinamide phosphoribosyltransferase (NAMPT) inhibitionGenomeQuantitative Profiling of Oncometabolites in Frozen and Formalin-Fixed Paraffin-Embedded Tissue Specimens by Liquid Chromatography Coupled with Tandem Mass Spectrometry
Bao X, Wu J, Shuch B, LoRusso P, Bindra RS, Li J. Quantitative Profiling of Oncometabolites in Frozen and Formalin-Fixed Paraffin-Embedded Tissue Specimens by Liquid Chromatography Coupled with Tandem Mass Spectrometry. Scientific Reports 2019, 9: 11238. PMID: 31375752, PMCID: PMC6677826, DOI: 10.1038/s41598-019-47669-5.Peer-Reviewed Original ResearchDNMT3A co-mutation in an IDH1-mutant glioblastoma
Fomchenko EI, Erson-Omay EZ, Zhao A, Bindra RS, Huttner A, Fulbright RK, Moliterno J. DNMT3A co-mutation in an IDH1-mutant glioblastoma. Molecular Case Studies 2019, 5: a004119. PMID: 31371348, PMCID: PMC6672028, DOI: 10.1101/mcs.a004119.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorBrain NeoplasmsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA Modification MethylasesEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticGlioblastomaGliomaHumansIsocitrate DehydrogenaseMaleMutationMutation, MissensePromoter Regions, GeneticConceptsIDH1-mutant glioblastomaEpigenetic controlHistone modificationsTranscriptional regulationDNA methylationExpression profilesGlioblastoma biologySomatic mutationsDe novoMutationsMutant glioblastomasTumor landscapeMutational profileTargeted therapeutic approachesGlioblastomaImportant roleMethylationDNMT3ABiologyGliomagenesisMissenseRegulationNovoPrimary brain tumorsTherapeutic approachesDefining an Intermediate-risk Group for Low-grade Glioma: A National Cancer Database Analysis
JAIRAM V, KANN BH, PARK HS, MICCIO JA, BECKTA JM, YU JB, PRABHU RS, GAO SJ, MEHTA MP, CURRAN WJ, BINDRA RS, CONTESSA JN, PATEL KR. Defining an Intermediate-risk Group for Low-grade Glioma: A National Cancer Database Analysis. Anticancer Research 2019, 39: 2911-2918. PMID: 31177129, DOI: 10.21873/anticanres.13420.Peer-Reviewed Original ResearchConceptsIntermediate-risk groupInferior overall survivalOverall survivalAdjuvant therapyLow-grade gliomasTumor sizePrognostic featuresMultivariate analysisPre-operative tumor sizeNational Cancer Database AnalysisNational Cancer DatabaseLow-risk patientsCohort of patientsKaplan-Meier methodPoor prognostic featuresGross total resectionHigh-risk groupPatterns of careAdditional prognostic featuresRTOG 9802Clinical factorsTotal resectionCancer DatabaseRisk groupsClinical classificationAssembling the brain trust: the multidisciplinary imperative in neuro-oncology
Ludmir EB, Mahajan A, Ahern V, Ajithkumar T, Alapetite C, Bernier-Chastagner V, Bindra RS, Bishop AJ, Bolle S, Brown PD, Carrie C, Chalmers AJ, Chang EL, Chung C, Dieckmann K, Esiashvili N, Gandola L, Ghia AJ, Gondi V, Grosshans DR, Harrabi SB, Horan G, Indelicato DJ, Jalali R, Janssens GO, Krause M, Laack NN, Laperriere N, Laprie A, Li J, Marcus KJ, McGovern SL, Merchant TE, Merrell KW, Padovani L, Parkes J, Paulino AC, Schwarz R, Shih HA, Souhami L, Sulman EP, Taylor RE, Thorp N, Timmermann B, Wheeler G, Wolden SL, Woodhouse KD, Yeboa DN, Yock TI, Kortmann RD, McAleer MF. Assembling the brain trust: the multidisciplinary imperative in neuro-oncology. Nature Reviews Clinical Oncology 2019, 16: 521-522. PMID: 31150024, DOI: 10.1038/s41571-019-0235-z.Peer-Reviewed Original ResearchRe: Catherine H. Marshall, Alexandra O. Sokolova, Andrea L. McNatty, et al. Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations. Eur Urol 2019;76:452–8
Liang J, Beckta JM, Bindra RS. Re: Catherine H. Marshall, Alexandra O. Sokolova, Andrea L. McNatty, et al. Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations. Eur Urol 2019;76:452–8. European Urology 2019, 76: e109-e110. PMID: 31080125, DOI: 10.1016/j.eururo.2019.04.041.Peer-Reviewed Original ResearchNanoparticle-mediated intratumoral inhibition of miR-21 for improved survival in glioblastoma
Seo YE, Suh HW, Bahal R, Josowitz A, Zhang J, Song E, Cui J, Noorbakhsh S, Jackson C, Bu T, Piotrowski-Daspit A, Bindra R, Saltzman WM. Nanoparticle-mediated intratumoral inhibition of miR-21 for improved survival in glioblastoma. Biomaterials 2019, 201: 87-98. PMID: 30802686, PMCID: PMC6451656, DOI: 10.1016/j.biomaterials.2019.02.016.Peer-Reviewed Original ResearchConceptsEfficient intracellular deliveryDelivery systemPeptide nucleic acidNanoparticle productsNanoparticlesIntracellular deliveryConvection-enhanced deliveryDifferent delivery systemsNucleic acidsSignificant therapeutic efficacyMiR-21 suppressionTherapeutic efficacyLocal deliveryDeliverySystemic toxicityBlock copolymersDistinct advantagesPolyglycerolMiR-21
2018
Pathologic Oxidation of PTPN12 Underlies ABL1 Phosphorylation in Hereditary Leiomyomatosis and Renal Cell Carcinoma
Xu Y, Taylor P, Andrade J, Ueberheide B, Shuch B, Glazer PM, Bindra RS, Moran MF, Linehan WM, Neel BG. Pathologic Oxidation of PTPN12 Underlies ABL1 Phosphorylation in Hereditary Leiomyomatosis and Renal Cell Carcinoma. Cancer Research 2018, 78: 6539-6548. PMID: 30297534, PMCID: PMC6279512, DOI: 10.1158/0008-5472.can-18-0901.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCell Line, TumorFumarate HydrataseGerm-Line MutationHumansLeiomyomatosisMetabolomeMetabolomicsModels, BiologicalNeoplastic Syndromes, HereditaryOxidation-ReductionPhosphorylationProtein BindingProtein Tyrosine Phosphatase, Non-Receptor Type 12Proto-Oncogene Proteins c-ablReactive Oxygen SpeciesSkin NeoplasmsUterine NeoplasmsThe Higher the Grade, the Bigger the Field
Beckta JM, Bindra RS. The Higher the Grade, the Bigger the Field. International Journal Of Radiation Oncology • Biology • Physics 2018, 102: 488-489. PMID: 30238899, DOI: 10.1016/j.ijrobp.2018.08.019.Peer-Reviewed Original ResearchKrebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair
Sulkowski PL, Sundaram RK, Oeck S, Corso CD, Liu Y, Noorbakhsh S, Niger M, Boeke M, Ueno D, Kalathil AN, Bao X, Li J, Shuch B, Bindra RS, Glazer PM. Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nature Genetics 2018, 50: 1086-1092. PMID: 30013182, PMCID: PMC6072579, DOI: 10.1038/s41588-018-0170-4.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksPGL/PCCDNA repair deficiency syndromeHomologous recombination DNA repair pathwayDNA repair pathwaysDouble-strand breaksHomologous recombination DNA repairSynthetic lethal targetingGenomic integrityDNA repairFumarate hydrataseMechanistic basisCancer predispositionFunction mutationsGermline lossKrebs cycleSuccinate dehydrogenaseHereditary paragangliomaRespectively1–3Ribose polymerase inhibitorsHereditary leiomyomatosisHereditary cancer syndromesCancer syndromesTumor cellsPolymerase inhibitorsResidual Convolutional Neural Network for Determination of IDH Status in Low- and High-grade Gliomas from MR Imaging
Chang K, Bai HX, Zhou H, Su C, Bi WL, Agbodza E, Kavouridis VK, Senders JT, Boaro A, Beers A, Zhang B, Capellini A, Liao W, Shen Q, Li X, Xiao B, Cryan J, Ramkissoon S, Ramkissoon L, Ligon K, Wen PY, Bindra RS, Woo J, Arnaout O, Gerstner ER, Zhang PJ, Rosen BR, Yang L, Huang RY, Kalpathy-Cramer J. Residual Convolutional Neural Network for Determination of IDH Status in Low- and High-grade Gliomas from MR Imaging. Clinical Cancer Research 2018, 24: clincanres.2236.2017. PMID: 29167275, PMCID: PMC6051535, DOI: 10.1158/1078-0432.ccr-17-2236.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBrainBrain NeoplasmsDatasets as TopicFemaleGliomaHumansImage Processing, Computer-AssistedIsocitrate DehydrogenaseMagnetic Resonance ImagingMaleMiddle AgedMutationNeoplasm GradingNeural Networks, ComputerPredictive Value of TestsPreoperative PeriodRetrospective StudiesYoung AdultConceptsResidual convolutional neural networkConvolutional neural networkNeural networkDeep learning techniquesTesting setNeural network modelMulti-institutional data setCancer Imaging ArchiveLearning techniquesTesting accuracyNetwork modelTraining setPrediction accuracyPreoperative radiographic dataClin Cancer ResData setsConventional MR imagingHospital of UniversityIsocitrate dehydrogenase (IDH) mutationPreoperative imagingLonger survivalWomen's HospitalGrade IINetworkTreatment decisionsResponse to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib
Marks AM, Bindra RS, DiLuna ML, Huttner A, Jairam V, Kahle KT, Kieran MW. Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib. Pediatric Blood & Cancer 2018, 65: e26969. PMID: 29380516, DOI: 10.1002/pbc.26969.Peer-Reviewed Original ResearchConceptsAnaplastic gangliogliomaBRAF/MEK inhibitor combinationsBRAF V600ESubsequent tumor responseDabrafenib/trametinibLarge clinical trialsSquamous cell carcinomaMEK inhibitor combinationsSignificant side effectsSignificant skin reactionsCell carcinomaCase reportSkin reactionsTumor responseClinical trialsBrain tumorsInhibitor combinationsSide effectsAdolescent femalesGangliogliomaTrametinibPrevious reactionsV600EMonotherapyRashYale Cancer Center Precision Medicine Tumor Board: two patients, one targeted therapy, different outcomes
Cecchini M, Walther Z, Sklar JL, Bindra RS, Petrylak DP, Eder JP, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: two patients, one targeted therapy, different outcomes. The Lancet Oncology 2018, 19: 23-24. PMID: 29304353, DOI: 10.1016/s1470-2045(17)30916-6.Peer-Reviewed Case Reports and Technical Notes