2019
Epigenetic priming prior to pembrolizumab in mismatch repair-proficient advanced colorectal cancer.
Murphy A, Walker R, Lutz E, Parkinson R, Ahuja N, Zheng L, Jaffee E, Azad N. Epigenetic priming prior to pembrolizumab in mismatch repair-proficient advanced colorectal cancer. Journal Of Clinical Oncology 2019, 37: 591-591. DOI: 10.1200/jco.2019.37.4_suppl.591.Peer-Reviewed Original ResearchArm BArm AColorectal cancerAdvanced CRC patientsMedian treatment cycleMMR-deficient CRCMMR-proficient tumorsLines of chemotherapyAdvanced colorectal cancerPre-treatment biopsiesPost-treatment biopsiesPredictors of responseEpigenetic therapyCTCAE v4.0CRC patientsImmune checkpointsMedian ageProficient tumorsRepeat biopsySingle institutionDisease progressionArm C.Arm CGrade 3Patients
2017
Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells
Siebenkäs C, Chiappinelli KB, Guzzetta AA, Sharma A, Jeschke J, Vatapalli R, Baylin SB, Ahuja N. Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells. PLOS ONE 2017, 12: e0179501. PMID: 28622390, PMCID: PMC5473589, DOI: 10.1371/journal.pone.0179501.Peer-Reviewed Original ResearchConceptsSubset of patientsOvarian cancer cell linesAntigen processingCancer cell linesImmune therapyCancer testisSolid tumorsCell linesCancer cellsCancer-testis antigensHost immune systemOvarian cancer cellsTreatment time pointsEpigenetic therapyRelevant low dosesPresentation machineryImmune cellsOvarian cancerAntigen presentationMurine modelTestis antigensInnovative therapiesImmune systemLow dosesTherapyCombination 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 patternsCombination 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 therapy in gastrointestinal cancer: the right combination
Abdelfatah E, Kerner Z, Nanda N, Ahuja N. Epigenetic therapy in gastrointestinal cancer: the right combination. Therapeutic Advances In Gastroenterology 2016, 9: 560-579. PMID: 27366224, PMCID: PMC4913338, DOI: 10.1177/1756283x16644247.Peer-Reviewed Original ResearchDNA methyltransferaseEpigenetic dysregulationEpigenetic drugsEpigenetic therapyCpG island methylator phenotypeDeoxyribonucleic acid methylationChromatin remodelingHistone modificationsCancer epigenomeEpigenetic reprogrammingWidespread epigenetic dysregulationCancer epigeneticsEpigenetic targetsCancer stem cellsHistone deacetylase inhibitorsMolecular biologyAcid methylationStem cellsDeacetylase inhibitorsDevelopment of drugsEpigeneticsGenetic mutationsMethylator phenotypeChemo resistanceEpigenetic sensitizationEpigenetic 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
A randomized phase II trial of epigenetic therapy following adjuvant treatment in patients with resected pancreatic cancer and high risk for recurrence.
Reiss K, Ahuja N, Baylin S, Mauro L, Linden S, White S, Laheru D, Herman J, Wolfgang C, Weiss M, Cameron J, Makary M, Azad N. A randomized phase II trial of epigenetic therapy following adjuvant treatment in patients with resected pancreatic cancer and high risk for recurrence. Journal Of Clinical Oncology 2015, 33: tps4144-tps4144. DOI: 10.1200/jco.2015.33.15_suppl.tps4144.Peer-Reviewed Original ResearchEpigenetic 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
Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers
Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, Stearns V, Pardoll DM, Davidson N, Jones PA, Slamon DJ, Baylin SB, Zahnow CA, Ahuja N. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 2014, 5: 587-598. PMID: 24583822, PMCID: PMC3996658, DOI: 10.18632/oncotarget.1782.Peer-Reviewed Original ResearchConceptsDNA methyltransferase inhibitorImmune gene setsImmune-stimulatory roleCytokines/chemokinesCancer-testis antigensGene expression subsetsMethyltransferase inhibitorEpigenetic therapyHuman epithelial cancersMechanism of actionCancer cell linesPrimary tumorGene Set Enrichment AnalysisImmunomodulatory pathwaysImmune regulationPotential therapyTestis antigensPatient biopsiesSolid tumorsEpithelial cancersMultiple cancersLow dosesTumor expression dataAntigen processingTherapyHarnessing 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