2023
A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer
Baretti M, Murphy A, Zahurak M, Gianino N, Parkinson R, Walker R, Lopez-Vidal T, Zheng L, Rosner G, Ahuja N, Kurt S, Azad N. A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer. Clinical Epigenetics 2023, 15: 74. PMID: 37120591, PMCID: PMC10149019, DOI: 10.1186/s13148-023-01485-x.Peer-Reviewed Original ResearchConceptsColorectal cancer patientsAdvanced colorectal cancer patientsImmune checkpoint inhibitor therapyMedian progression-free survivalDurable partial responseHematological adverse eventsMMR-proficient tumorsCheckpoint inhibitor therapyAdvanced colorectal cancerProgression-free survivalImmune cell infiltrationHistone deacetylasesImmunologic shiftCheckpoint inhibitorsRECIST criteriaAdverse eventsCheckpoint therapyOverall survivalPartial responseInhibitor therapyMedian ageColorectal cancerFurther mechanistic investigationsCancer patientsCell infiltration
2020
Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance
Olino K, Park T, Ahuja N. Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance. Seminars In Cancer Biology 2020, 65: 114-122. PMID: 31911188, DOI: 10.1016/j.semcancer.2020.01.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsResponse ratePeripheral T-cell lymphomaTriple-negative breast cancerLarge B-cell lymphomaDurable response rateEffective standard therapyDeath protein 1Solid organ tumorsInhibitory immune receptorsT-cell lymphomaNegative breast cancerB-cell lymphomaAdvanced malignanciesMost patientsStandard therapyClinical efficacyCommon malignancyHepatobiliary cancersTherapeutic optionsNeck cancerOrgan tumorsInitial respondersOvarian cancerProstate cancerBreast cancer
2019
Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood
Eissa MAL, Lerner L, Abdelfatah E, Shankar N, Canner JK, Hasan NM, Yaghoobi V, Huang B, Kerner Z, Takaesu F, Wolfgang C, Kwak R, Ruiz M, Tam M, Pisanic TR, Iacobuzio-Donahue CA, Hruban RH, He J, Wang TH, Wood LD, Sharma A, Ahuja N. Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood. Clinical Epigenetics 2019, 11: 59. PMID: 30953539, PMCID: PMC6451253, DOI: 10.1186/s13148-019-0650-0.Peer-Reviewed Original ResearchConceptsStage IIB diseasePancreatic cancerIIB diseaseStage IIACA 19Stage IBiomarker panelBlood-based biomarker panelPre-operative CA 19Stage I patientsCell-free tumor DNAHigh-risk populationPotential blood biomarkersMost pancreatic cancersBackgroundDespite improvementsCurative resectionSurgical resectionI patientsTwo-gene panelPancreas cancerBlood biomarkersCurative potentialCancer managementAdvanced stageCombination panel
2018
A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan
Lee V, Wang J, Zahurak M, Gootjes E, Verheul H, Parkinson R, Kerner Z, Sharma A, Rosner G, De Jesus-Acosta A, Laheru D, Le DT, Oganesian A, Lilly E, Brown T, Jones P, Baylin S, Ahuja N, Azad N. A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan. Clinical Cancer Research 2018, 24: 6160-6167. PMID: 30097434, DOI: 10.1158/1078-0432.ccr-18-0421.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerNeutropenic feverMetastatic colorectal cancer patientsDurable partial responseMost common toxicitiesDose-escalation studyColorectal cancer patientsInjection site reactionsOngoing phase IIPhase I trialInitial disease progressionCycles of treatmentCommon toxicitiesDrain infectionEvaluable patientsStable diseaseColonic obstructionPartial responseI trialMulticenter trialColorectal cancerGastrointestinal cancerSite reactionsCancer patientsDisease progressionA novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent
Thakar M, Hu Y, Morreale M, Lerner L, Lin W, Sen R, Cai Y, Karunasena E, Thakar M, Saggi S, Keer H, Ahuja N. A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent. PLOS ONE 2018, 13: e0199130. PMID: 29927979, PMCID: PMC6013229, DOI: 10.1371/journal.pone.0199130.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaDNA methyltransferase 1Chemotherapeutic agent irinotecanEpigenetic modulating agentsPDAC cell linesCell viabilityMechanism of actionSystemic chemotherapyCancer mortalityChemotherapy responseDuctal adenocarcinomaChemotherapy agentsEpigenetic sensitizationModulating agentsGuadecitabineAdditional studiesPancreatic cellsSerial concentrationsRest periodCell linesNanomolar concentrationsImproved responseEpigenetic modulatorsSensitizationMethyltransferase 1Epigenetics of gastrointestinal diseases: notes from a workshop
Marks DL, Olson RL, Urrutia R, Billadeau DD, Roy N, Calin GA, Fabbri M, Koutsioumpa M, Iliopoulos D, Ordog T, Huebert R, Sarmento O, Bamidele AO, Faubion W, Lomberk GL, Siveke J, Ahuja N, Iovanna J, Hlady RA, Robertson K, Kisiel J, Pin CL, Fernandez-Zapico ME. Epigenetics of gastrointestinal diseases: notes from a workshop. Epigenetics 2018, 13: 449-457. PMID: 30056798, PMCID: PMC6140811, DOI: 10.1080/15592294.2018.1464351.Peer-Reviewed Original ResearchMeSH KeywordsDNA MethylationEpigenesis, GeneticGastrointestinal DiseasesGenetic HeterogeneityGenetic MarkersHumansTranslational Research, BiomedicalDNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk
Xie W, Kagiampakis I, Pan L, Zhang YW, Murphy L, Tao Y, Kong X, Kang B, Xia L, Carvalho FLF, Sen S, Yen R, Zahnow CA, Ahuja N, Baylin SB, Easwaran H. DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk. Cancer Cell 2018, 33: 309-321.e5. PMID: 29438699, PMCID: PMC5813821, DOI: 10.1016/j.ccell.2018.01.008.Peer-Reviewed Original ResearchConceptsDevelopmental genesDNA methylation patternsPromoter hypermethylation eventsEpigenetic patternsMethylation gainMethylation patternsMethylation changesHypermethylation eventsEpigenetic changesTissue agingSenescenceMetabolic regulatorTissue typesGenesTransformation potentialCellsHypermethylationRegulatorCancer risk
2017
The Roles of DNA Methylation in the Stages of Cancer
McMahon KW, Karunasena E, Ahuja N. The Roles of DNA Methylation in the Stages of Cancer. The Cancer Journal 2017, 23: 257-261. PMID: 28926425, PMCID: PMC5657558, DOI: 10.1097/ppo.0000000000000279.Peer-Reviewed Original ResearchCombination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study
Connolly RM, Li H, Jankowitz RC, Zhang Z, Rudek MA, Jeter SC, Slater SA, Powers P, Wolff AC, Fetting JH, Brufsky A, Piekarz R, Ahuja N, Laird PW, Shen H, Weisenberger DJ, Cope L, Herman JG, Somlo G, Garcia AA, Jones PA, Baylin SB, Davidson NE, Zahnow CA, Stearns V. Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study. Clinical Cancer Research 2017, 23: 2691-2701. PMID: 27979916, PMCID: PMC5457329, DOI: 10.1158/1078-0432.ccr-16-1729.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerObjective response rateCombination epigenetic therapyEstrogen receptorEndocrine therapyPrimary endpointPartial responseMulticenter phase II studyEpigenetic therapyAdditional partial responsesHormone-resistant diseasePhase II studyTime of progressionBreast cancer modelClin Cancer ResHistone deacetylase inhibitorsImportant therapeutic targetPosttreatment biopsiesTNBC cohortII studyBreast cancerDNA methyltransferase inhibitorTherapeutic targetResponse rateCancer modelEpigenetic therapy and chemosensitization in solid malignancy
Ronnekleiv-Kelly SM, Sharma A, Ahuja N. Epigenetic therapy and chemosensitization in solid malignancy. Cancer Treatment Reviews 2017, 55: 200-208. PMID: 28431263, DOI: 10.1016/j.ctrv.2017.03.008.Peer-Reviewed Original ResearchConceptsCombination therapyEpigenetic therapySpecific hematologic malignanciesCertain solid tumorsHistone deacetylase inhibitorsDurable responsesSystemic therapyPatient subsetsSolid malignanciesHematologic malignanciesOvarian cancerBreast cancerDNA methyltransferase inhibitorEpigenetic changesSolid tumorsDeacetylase inhibitorsStandard chemotherapeuticsTherapyClinical potentialCancer cellsTrialsNSCLCMalignancyMethyltransferase inhibitorHypermethylation patternsEpigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer
Yi JM, Kang EJ, Kwon HM, Bae JH, Kang K, Ahuja N, Yang K. Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer. Oncotarget 2017, 5: 26600-26612. PMID: 28460450, PMCID: PMC5432282, DOI: 10.18632/oncotarget.15722.Peer-Reviewed Original ResearchConceptsCpG island hypermethylationTumor suppressorEctopic expressionPancreatic cancer cellsIsland hypermethylationPancreatic cancer cell linesHuman cancersPutative target genesCancer cell linesNumber of miRNAsChromosome condensation 2Role of miRNAsCell linesMolecular functional roleCancer cellsCpG island methylationPotential tumor suppressorTarget genesEpigenetic alterationsGene expressionMalignant human cancersIsland methylationDirect targetLuciferase reporterFunctional roleCombination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study
Azad NS, el-Khoueiry A, Yin J, Oberg AL, Flynn P, Adkins D, Sharma A, Weisenberger DJ, Brown T, Medvari P, Jones PA, Easwaran H, Kamel I, Bahary N, Kim G, Picus J, Pitot HC, Erlichman C, Donehower R, Shen H, Laird PW, Piekarz R, Baylin S, Ahuja N. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study. Oncotarget 2017, 5: 35326-35338. PMID: 28186961, PMCID: PMC5471058, DOI: 10.18632/oncotarget.15108.Peer-Reviewed Original ResearchConceptsCombination epigenetic therapyMetastatic colorectal cancerRECIST responseCRC patientsMedian progression-free survivalCycles of therapySignificant clinical activityMetastatic CRC patientsProgression-free survivalSubset of patientsM2 days 1Serial tumor biopsiesMulti-institutional studyHistone deacetylase inhibitor entinostatEpigenetic therapyColorectal cell linesSubcutaneous azacitidinePrimary endpointPrior therapyLiver involvementOverall survivalTolerable therapySerial biopsiesColorectal cancerClinical activity
2016
Epigenetic Therapeutics: A New Weapon in the War Against Cancer
Ahuja N, Sharma AR, Baylin SB. Epigenetic Therapeutics: A New Weapon in the War Against Cancer. Annual Review Of Medicine 2016, 67: 73-89. PMID: 26768237, PMCID: PMC4937439, DOI: 10.1146/annurev-med-111314-035900.Peer-Reviewed Original ResearchConceptsEpigenetic therapyPrimary base sequenceNucleosome positioningEpigenetic regulationCellular regulationHeritable patternsEpigenetic mechanismsDNA methylationExplosion of discoveriesGene expressionCancer initiationBase sequenceEpigenomeRegulationFrequent mutationsGenetic abnormalitiesNormal maturationTumor cellsPotent toolChromatinCellsNeoplastic cellsGenesMethylationProtein
2015
Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer
Calmon MF, Jeschke J, Zhang W, Dhir M, Siebenkäs C, Herrera A, Tsai HC, O'Hagan HM, Pappou EP, Hooker CM, Fu T, Schuebel KE, Gabrielson E, Rahal P, Herman JG, Baylin SB, Ahuja N. Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer. Epigenetics 2015, 10: 622-632. PMID: 25985363, PMCID: PMC4622480, DOI: 10.1080/15592294.2015.1050173.Peer-Reviewed Original ResearchConceptsNeurofilament medium polypeptideNeurofilament heavy polypeptideDNA methylation-associated silencingDNA methylation-mediated silencingNeurofilament genesMethylation-mediated silencingMethylation-associated silencingMethylation-mediated inactivationGo/G1 phaseEpigenetic silencingMedium polypeptideEpigenetic inactivationCell cycleMajor subunitBreast cancer cellsCell typesGenesSilencingHeavy polypeptideG1 phaseFunctional significanceCandidate DNAMature neuronsCancer cellsPolypeptideEpigenetic therapy for solid tumors: from bench science to clinical trials
Juo YY, Gong XJ, Mishra A, Cui X, Baylin SB, Azad NS, Ahuja N. Epigenetic therapy for solid tumors: from bench science to clinical trials. Epigenomics 2015, 7: 215-235. PMID: 25942532, DOI: 10.2217/epi.14.73.Peer-Reviewed Original ResearchConceptsEpigenetic agentsCpG island promotersSolid tumorsGlobal DNA methylationOptimal patient selectionTumor suppressor geneNew therapeutic modalitiesChromatin changesCancer epigenomeHistone deacetylase inhibitorsDNA methylationDNA methyltransferaseEpigenetic therapyHormonal therapyDrug regimenSuppressor genePatient selectionFuture trialsHematologic malignanciesRecent trialsClinical trialsSignificant efficacyTherapeutic modalitiesPhenotype changesDeacetylase inhibitors
2014
CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas
Sun L, Guzzetta AA, Fu T, Chen J, Jeschke J, Kwak R, Vatapalli R, Baylin SB, Iacobuzio-Donahue CA, Wolfgang CL, Ahuja N. CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas. Epigenetics 2014, 9: 738-746. PMID: 24518818, PMCID: PMC4063833, DOI: 10.4161/epi.28082.Peer-Reviewed Original ResearchConceptsCpG island methylator phenotypeSporadic duodenal adenomasDuodenal adenomasBRAF mutationsVillous typeMethylator phenotypeCIMP-high statusPeriampullary locationAggressive managementDuodenal adenocarcinomaClinicopathologic featuresColorectal cancerColorectal adenomasKRAS mutationsHigh riskAdenomasMLH1 methylationCIMP statusCancerous lesionsOlder ageP16 methylationTumorsMalignancyInfrequent eventRole of methylationHarnessing the potential of epigenetic therapy to target solid tumors
Ahuja N, Easwaran H, Baylin SB. Harnessing the potential of epigenetic therapy to target solid tumors. Journal Of Clinical Investigation 2014, 124: 56-63. PMID: 24382390, PMCID: PMC3871229, DOI: 10.1172/jci69736.Peer-Reviewed Original Research
2013
Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer
Yi JM, Guzzetta AA, Bailey VJ, Downing SR, Van Neste L, Chiappinelli KB, Keeley BP, Stark A, Herrera A, Wolfgang C, Pappou EP, Iacobuzio-Donahue CA, Goggins MG, Herman JG, Wang TH, Baylin SB, Ahuja N. Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer. Clinical Cancer Research 2013, 19: 6544-6555. PMID: 24088737, PMCID: PMC4310572, DOI: 10.1158/1078-0432.ccr-12-3224.Peer-Reviewed Original ResearchADAM ProteinsADAMTS1 ProteinBiomarkers, TumorCarcinoma in SituCell Line, TumorCell MovementCell ProliferationCpG IslandsDNADNA MethylationDNA-Binding ProteinsEarly Detection of CancerEpigenesis, GeneticFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMolecular Diagnostic TechniquesPancreatic NeoplasmsPromoter Regions, GeneticProportional Hazards ModelsSensitivity and SpecificitySequence Analysis, DNATranscription FactorsTranscriptomeExtraction and processing of circulating DNA from large sample volumes using methylation on beads for the detection of rare epigenetic events
Keeley B, Stark A, Pisanic TR, Kwak R, Zhang Y, Wrangle J, Baylin S, Herman J, Ahuja N, Brock MV, Wang TH. Extraction and processing of circulating DNA from large sample volumes using methylation on beads for the detection of rare epigenetic events. Clinica Chimica Acta 2013, 425: 169-175. PMID: 23911908, PMCID: PMC3963364, DOI: 10.1016/j.cca.2013.07.023.Peer-Reviewed Original Research
2012
A DNA hypermethylation module for the stem/progenitor cell signature of cancer
Easwaran H, Johnstone SE, Van Neste L, Ohm J, Mosbruger T, Wang Q, Aryee MJ, Joyce P, Ahuja N, Weisenberger D, Collisson E, Zhu J, Yegnasubramanian S, Matsui W, Baylin SB. A DNA hypermethylation module for the stem/progenitor cell signature of cancer. Genome Research 2012, 22: 837-849. PMID: 22391556, PMCID: PMC3337430, DOI: 10.1101/gr.131169.111.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorChromatinCluster AnalysisCpG IslandsDNA MethylationEmbryonic Stem CellsEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmGenes, RegulatorHistonesHumansMesenchymal Stem CellsNeoplasmsOligonucleotide Array Sequence AnalysisOsteoblastsPolycomb-Group ProteinsPromoter Regions, GeneticRepressor ProteinsSequence Analysis, DNAConceptsEmbryonic stem cellsBivalent chromatinDevelopmental regulatorsPcG target genesKey developmental regulatorsGenome-wide analysisSubset of genesPolycomb repressor complexesStem cellsAdult stem/progenitor cellsStem-like stateStem/progenitor cellsTranscription statePcG genesRepressor complexNormal stem cellsChromatin statusHypermethylated genesTarget genesDNA hypermethylationCancer genesGlobal methylationChromatinGenesMethylation status